Abstract
Background
Growing evidence reported that linc00473 was abnormally expressed in various tumor tissues, elevated linc00473 expression manifested unsatisfactory survival outcome. Due to the inconsistent results from different research, a meta-analysis was executed to examine the link between linc00473 level and cancer prognosis.
Methods
An exhaustive search was made from relative databases, suitable publications were enrolled based on the inclusion and exclusion criteria. The overall literature quality was assessed based on the Newcastle-Ottawa Scale (NOS) score. Relevant data was extracted such as overall survival (OS), TNM stage and lymph node metastasis (LNM) and so on. To determine the stability and dependability of the aggregated results, sensitivity analysis was implemented, while Begg’s analysis was applied to examine possible publication bias.
Results
This meta-analysis encompassed 15 publications totaling 1144 patients. Linc00473 showed elevation in most tumor tissues, with heightened linc00473 expression suggesting inferior cancer prognosis (HR: 1.850, 95% confidence interval (CI): 1.230–2.80, P = 0.003). Subgroup analysis findings revealed comparable negative prognostic implications in the respiratory system (HR: 2.23, 95%CI: 1.39–3.58, P = 0.0008), reproductive system (HR: 3.19, 95%CI: 2.00–5.11, P < 0.00001) and additional systems (HR: 2.56, 95%CI: 1.37–4.80, P = 0.003). Moreover, elevated linc00473 expression correlated with advanced TNM stage (OR: 3.78, 95%CI: 2.75–5.19, P < 0.00001), distant metastasis (OR: 4.61, 95%CI: 2.53–8.39, P < 0.00001), increased tumor size (OR: 3.10, 95%CI: 2.13–4.50, P < 0.00001) and poor histological grade (OR: 1.85, 95%CI: 1.29–2.67, P = 0.0009). Sensitivity analysis confirmed the overall results’ stability and reliability, while Begg’s analysis indicated no substantial publication bias existed among the examined publications.
Conclusion
High linc00473 expression has been detected across diverse tumor tissues, high linc00473 expression implies poor cancer prognosis, linc00473 potentially functions as a prospective therapeutic target and prognostic indicator. More high-quality documents were wished to implement to support the results of this study.
Supplementary Information
The online version contains supplementary material available at 10.1007/s12672-025-03999-7.
Keywords: Long non-coding RNA 00473, Cancer, Prognosis, Meta-analysis
Introduction
In recent decades, cancer has significantly affected human physical and mental health, it is estimated that in 2020, there was almost 19.3 million new cancer cases and nearly 9.7 million cancer deaths worldwide, equivalent to about 52,876 new cases and nearly 26,575 deaths per day [1]. In males, lung, prostate, and colorectal cancers represent the predominant causes of mortality, whereas in females, lung, breast, and colorectal cancers constitute the leading sources of death [2]. Cancer not only poses a great economic burden but also causes immense mental pressure on people worldwide every year. Unfortunately, many cancer patients receive their diagnosis during intermediate or advanced stages of the disease, as the early symptoms are often not apparent, resulting in missed opportunities for surgical treatment [3]. Although chemotherapy, radiotherapy, targeted therapy and immunotherapy were routinely applied to patients with advanced cancer, the survival outlook for individuals with advanced cancer continues to be disappointing [4], and researchers urgently need to explore new treatment targets and prognostic markers [5, 6].
In recent years, with advancements in molecular biology, numerous long non-coding RNA has been documented to display abnormal expression patterns in tumor cells and exhibit notable associations with cancer initiation and progression [7]. LncRNA is a kind of small molecular biomarkers with more than 200 nucleotides that lack the ability of protein coding, which accounts for a large proportion in cells [8]. With the deepening of research, growing evidence shows that lncRNA participates in a series of cell biological processes, and closely related to the progress of cancer. lncRNA was revealed to be affect gene expression at gene replication regulation, transcription level and post-transcriptional modification level [9, 10]. For instance, Zhu et al. demonstrates that lncSNHG15 facilitates the proliferation, migration and invasion of colorectal cancer through enhancing the Wnt/β-catenin signaling pathway [11], Lan et al. reported that elevated expression of lncPVT1 promotes the migration and invasion while reducing apoptosis in hepatoma cells through functioning as a sponge for miR-186-5p and diminishing its expression [12].
Linc00473 is a type of lncRNA consisting of more than 200 nucleotides that was initially found to be highly expressed in Fibrolamellar carcinoma (FLC) cells [13]. Over the following years, researchers discovered that linc00473 has aberrant expression in various types of tumor cells [14–16]. Although linc00473 lacks the ability to code for proteins, it has been demonstrated to serve a pivotal function in the progression of diverse cancers, enhancing cell proliferation, migration, invasion, suppressing apoptosis and facilitating platinum resistance [17–19]. Growing research has investigated the link between abnormal linc00473 levels and cancer prognosis, and increasing evidence suggests that elevated linc00473 expression predicts poor prognosis across various cancers [20–22]. However, small sample sizes has prevented some studies from finding significant relationships between linc00473 level and cancer prognosis, leading to different conclusions. Therefore, a meta-analysis was executed to examine the association between the linc00473 level and the survival and prognosis of different cancers, aiming to provide new targets and prognostic markers for cancer treatment. This article adheres to the PRISMA reporting checklist.
Materials and methods
Publication search and selection
We searched the relevant articles comprehensively in accordance with the preferred reporting item of the system evaluation and meta-analysis (PRISMA) based on PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI) and Wanfang Database from inception to November 1, 2022. The search term was defined to (“LINC00473” OR “long non-coding RNA 00473” OR “lnc00473”) AND (“Carcinoma” OR “cancer” OR “tumor” OR “prognosis” OR “survival prognosis”). The references of encompassed studies were also thoroughly examined to extract valuable data.
Inclusion and exclusion criteria
Research articles were included based on meeting these specific requirements: (a) Examined the association between linc00473 expression levels and cancer patient prognosis. (b) Stratified patients into high and low linc00473 expression groups according to measured expression values. (c) Include primary outcome indicators (overall survival, progression-free survival or relapse-free survival) or secondary outcome parameters (TNM stage, LNM, tumor size, etc.) (d) with enough data to summarize statistics. Exclusion criteria include the following items: (a) The correlation between the linc00473 level and cancer patient outcomes was not evaluated. (b) The subjects of the experiment are animals rather than patients. (c) Insufficient data or data unavailable. (d) meta-analysis, review, case report, meeting summary and so on.
Data extraction
For each appropriate publication, two researchers independently extracted clinical features, including the first author’s name, year of publication, cancer type, number of patients, reference gene, cut-off value, and other basic clinical features. As for the prognostic data like OS, PFS, DFS, RFS, HR with 95% CI was extracted, some primary studies simply exhibit survival curve and the sample size of high linc00473 expression and the sample size of low linc00473 expression, the software of Engauge Digitizer tool (v 4.1) was applied and the validated method was followed [23]. Additionally, OR with 95%CI was also extracted for other clinical data such as TNM stage, LNM, DM, tumor size, histological grade, invasion depth, age and gender.
Quality assessment for included studies
The quality assessment of selected studies utilized the Newcastle-Ottawa scale (NOS), which evaluates based on three primary categories (Selection, Comparability and Outcome) and eight second items (Adequate of case definition, Representativeness of the cases, Selection of Controls, Definition of Controls, Comparability of cases and controls, Ascertainment of exposure, Same method of ascertainment and non-Response rate). Independent evaluation by two investigators determined that studies scoring 6–9 points qualified for inclusion, whereas those scoring below 6 points were deemed unsuitable for incorporation in the analysis [24].
Statistical analysis
The statistical analysis for this investigation was executed utilizing Review Manager 5.4.0 version and STATA 12.0 version analytical platforms. HR with 95%CI were combined to evaluate the link between linc00473 level and cancer prognosis encompassing OS, PFS, DFS and RFS. The OR with 95%CI were also pooled to evaluate the association between linc00473 expression and clinicopathologic parameters such as TNM stage, LNM, tumor size and so on. The P-value and I square were used to evaluate the level of significance of heterogeneity among enrolled studies. When the P-value exceeds 0.05 and the I-square falls below 50%, it indicates insignificant heterogeneity across studies, warranting the application of the fixed effect model. In cases where the P-value falls below 0.05 and the I-square exceeds 50%, substantial heterogeneity exists between incorporated studies, necessitating the implementation of the random effect model, followed by subgroup analysis per the patient numbers, cut-off values, HR statistics, and cancer categories. To determine whether individual study outcomes substantially influence the overall findings, sensitivity analysis was conducted. Publication bias assessment among the incorporated studies utilized Begg’s test through STATA software.
Results
Publication inclusion and selection
The preliminary search yielded 137 publications, and subsequent screening identified 18 duplicate entries, 86 articles lacking investigation into linc00473 expression-prognosis correlation in cancer, 5 review articles, 6 articles with insufficient data or failure to meet the inclusion criteria, 4 bioinformatics articles, and 3 articles not written in English. The final analysis incorporated 15 eligible studies involving 1144 patients (Fig. 1).
Fig. 1.
The flow diagram of the eligible studies
Basic characteristics of inclusion study
15 publications with 11 cancer types were finally investigated, comprising esophageal squamous cell carcinoma (ESCC) [25, 26], lung cancer [22, 27], breast cancer [28, 29], hepatocellular carcinoma [30], cervical cancer [15], colorectal cancer [31], glioma [32], pancreatic cancer [33], cholangiocarcinoma [17], head and neck squamous cell carcinoma (HNSCC) [34] and gastric cancer [14, 35] (Table 1). All patients were from China, with individual research sample sizes varying between 31 and 135 subjects. In general, linc00473 is highly expressed in enrolled 11 cancer types, the reference genes of 15 studies were all GAPDH. As for cut-off value, 7 studies used a median expression value. 3 articles adopted multivariate analysis, and 12 articles adopted univariate analysis. Per the NOS score, all the included articles were higher than 6, suggesting that all articles could be utilized to examine the link between linc00473 level and cancer patient outcomes (Table 2).
Table 1.
Basic features of the publications included in this meta-analysis (n = 15)
| Author | Year | Cancer type | Sample | Gene expression | Reference gene | Cut-off value | HR and 95%CI | Follow-up (month) | NOS score |
|---|---|---|---|---|---|---|---|---|---|
| Chen WZ | 2019 | ESCC | 96 | Upregulated | GAPDH | Mean | 2.12 (1.04–4.34) | 60 | 8 |
| Niu LG | 2019 | BC | 60 | Upregulated | GAPDH | Mean | 2.56 (1.19–5.51) | 48 | 8 |
| Huang LN | 2020 | CCA | 60 | Upregulated | GAPDH | Median | 2.352(1.302–4.876) | 60 | 9 |
| Qin PY | 2020 | NSCLC | 72 | Upregulated | GAPDH | Mean | 1.92 (1.03–3.56) | 60 | 7 |
| Xu SH | 2021 | NSCLC | 58 | Upregulated | GAPDH | Mean | 2.74 (1.33–5.66) | 60 | 7 |
| Shi C | 2017 | CC | 80 | Upregulated | GAPDH | Median | 3.97 (1.84–8.55) | 36 | 7 |
| Wu HZ | 2020 | CRC | 135 | Upregulated | GAPDH | Median | 0.658 (0.418–1.031) | 108 | 8 |
| Bai J | 2019 | BC | 122 | Upregulated | GAPDH | Median | 3.215 (1.255–4.752) | 60 | 9 |
| Wang X | 2020 | Glioma | 40 | Upregulated | GAPDH | Median | 2.92 (1–8.54.54) | 52 | 8 |
| LiuWH | 2020 | ESCC | 46 | Upregulated | GAPDH | Mean | - | - | 7 |
| Han PB | 2018 | HNSCC | 78 | Upregulated | GAPDH | Mean | 2.39 (1.10–5.18) | 60 | 7 |
| Hao XF | 2020 | PC | 54 | Upregulated | GAPDH | Median | 2.00 (1.14–3.53) | 16 | 8 |
| Zhuo SS | 2021 | GC | 53 | Upregulated | GAPDH | Mean | - | - | 7 |
| Zhang W | 2018 | GC | 120 | Upregulated | GAPDH | Median | 0.39 (0.233–0.656) | 72 | 9 |
| Chen H | 2018 | HCC | 70 | Upregulated | GAPDH | Median | 1.75 (0.93–3.29) | 52 | 9 |
No.: number; NSCLC: non-small cell lung cancer; HCC: hepatocellular carcinoma; CRC: colorectal cancer; PC: pancreatic cancer; BC: breast cancer; CC: Cervical cancer; GC: gastric cancer; NA: not available; qRT-PCR: quantitative reverse transcription-polymerase chain reaction; ESCC: esophageal squamous cell carcinoma; CCA: cholangiocarcinoma; HNSCC: head and neck squamous cell carcinoma; HR: hazard ratio; NOS: Newcastle-Ottawa scale; CI: confidence interval; GAPDH: glyceraldehyde-3-phosphate dehydrogenase
Table 2.
Quality assessment of eligible studies Newcastle-Ottawa scale (NOS) score
| Author | Country | Selection | Comparability | Outcome | Total | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adequate of case definition | Representativeness of the cases | Selection of Controls | Definition of Controls | Comparability of cases and controls | Ascertainment of exposure | Same method of ascertainment | Non-Response rate | |||
| Huang LN (2020) | China | * | * | * | * | ** | * | * | * | 9 |
| Xu SH (2021) | China | * | * | * | * | * | - | * | * | 7 |
| Qin PY (2018) | China | * | * | * | * | * | - | * | * | 7 |
| Chen H (2018) | China | * | * | * | * | ** | * | * | * | 9 |
| Shi C (2017) | China | * | * | * | * | * | * | * | - | 7 |
| Wu HZ (2020) | China | * | * | * | * | ** | * | * | NA | 8 |
| Niu LG (2019) | China | * | * | * | * | * | * | * | * | 9 |
| Bai J (2019) | China | * | * | * | * | ** | * | * | * | 9 |
| Chen WZ (2019) | China | * | * | * | * | * | * | * | * | 8 |
| Liu WH (2020) | China | * | * | * | * | * | * | * | - | 7 |
| Han PB (2018) | China | * | * | * | * | * | * | - | * | 7 |
| Zhuo SS (2021) | China | * | * | * | * | * | * | * | NA | 7 |
| Zhang W (2015) | China | * | * | * | * | ** | * | * | * | 9 |
| Hao XF (2020) | China | * | * | * | * | * | * | * | * | 8 |
The link between the linc00473 level and OS
13 publications encompassing 1045 subjects documented the link between linc00473 level and cancer outcomes. Analysis demonstrated a notable positive association linking elevated linc00473 level to unfavorable survival results (HR: 1.850, 95%CI: 1.230–2.80, P = 0.003) (Fig. 2). Considering the significant heterogeneity (I2 = 80, P < 0.0001), the random effect model was applied, and the subgroup analysis was performed per the cancer type, analysis method, HR statistics, subject quantity, Cut-off threshold, Follow-up (month) and NOS score. The marked positive correlation could also be uncovered between high linc00473 expression and worse cancer outcomes in respiratory system (HR: 2.23, 95%CI: 1.39–3.58, P = 0.0008), reproductive system (HR: 3.19, 95%CI: 2.00–5.11.00.11, P < 0.00001), other system (HR: 2.56, 95%CI: 1.37–4.80, P = 0.003), the subgroup served mean value as cut-off value (HR: 2.08, 95%CI: 1.43–2.73, P < 0.001), the subgroup of NOS score is 9 (HR: 2.79, 95%CI: 1.54–4.04, P < 0.001) (Table 3). Meanwhile, the association between high linc00473 expression and cancer prognosis in another subgroup fail to get marked significance, more high-quality evidence is required to support and supplement the conclusion of this study (Table 3).
Fig. 2.
Forest plot displayed the link between linc00473 level and overall survival (OS) in cancers. Review Manager 5.4.0 version was applied, HR with 95%CI were combined to evaluate the link between linc00473 level and cancer prognosis encompassing OS. Analysis demonstrated a notable positive association linking elevated linc00473 level to unfavorable survival results (HR: 1.850, 95%CI: 1.230–2.80, P = 0.003). Considering the significant heterogeneity (I2 = 80, P < 0.0001), the random effect model was applied, and the subgroup analysis was performed per the cancer type, analysis method, HR statistics, subject quantity, Cut-off threshold, Follow-up (month) and NOS score. The marked positive correlation could also be uncovered between high linc00473 expression and worse cancer outcomes in respiratory system (HR: 2.23, 95%CI: 1.39–3.58, P = 0.0008), reproductive system (HR: 3.19, 95%CI: 2.00–5.11.00.11, P < 0.00001), other system (HR: 2.56, 95%CI: 1.37–4.80, P = 0.003)
Table 3.
Pooled HRs of overall survival of patients with increased linc00473 expression
| Subgroup analysis | No. of studies | No. of patients | Pooled HR (95% CI) | Heterogeneity | ||
|---|---|---|---|---|---|---|
| Fixed | Random | I2(%) | P-value | |||
| OS | 13 | 1045 | 1.540 (1.280–1.840) | 1.850 (1.230–2.80) | 80 | < 0.0001 |
| Cancer type | ||||||
| Digestive system | 6 | 535 | 1.11 (0.88–1.39) | 1.26 (0.67–2.35) | 86 | < 0.0001 |
| Respiratory system | 2 | 130 | 2.23 (1.39–3.58) | 2.23 (1.39–3.58) | 0 | 0.46 |
| Reproductive system | 3 | 262 | 3.19 (2.00–5.11.00.11) | 3.19 (2.00–5.11.00.11) | 0 | 0.73 |
| Other system | 2 | 118 | 2.56 (1.37–4.80) | 2.56 (1.37–4.80) | 0 | 0.77 |
| Analysis method | ||||||
| Multivariate analysis | 3 | 302 | 0.46 (0.25–0.67) | 1.84 (−0.14-3.81) | 86 | 0.001 |
| Univariate analysis | 10 | 743 | 1.00 (0.73–1.27) | 1.93 (1.20–2.66) | 61 | 0.006 |
| HR statistics | ||||||
| Direction | 3 | 302 | 0.46 (0.25–0.67) | 1.84 (−0.14-3.81) | 86 | 0.001 |
| Indirection | 10 | 743 | 1.00 (0.73–1.27) | 1.93 (1.20–2.66) | 61 | 0.006 |
| Number of patients | ||||||
| Less than 100 | 10 | 668 | 2.15 (1.62–2.68) | 2.15 (1.62–2.68) | 0 | 0.982 |
| More than 100 | 3 | 377 | 0.50 (0.33–0.68) | 0.75 (0.19–1.31) | 82.3 | 0.003 |
| Cut-off value | ||||||
| Median | 7 | 611 | 0.56 (0.39–0.73) | 1.33 (0.70–1.96) | 77.5 | < 0.0001 |
| Mean | 6 | 434 | 2.08 (1,43-2.73.73) | 2.08 (1,43-2.73.73) | 0 | 0.963 |
| Follow-up (month) | ||||||
| Not less than 60 month | 8 | 741 | 0.59 (0.42–0.76) | 1.44 (0.85–2.04) | 76.9 | < 0.0001 |
| Less than 60 month | 5 | 304 | 2.10 (1.35–2.85) | 2.10 (1.35–2.85) | 0 | 0.752 |
| NOS score | ||||||
| 9 | 2 | 182 | 2.79 (1.54–4.04) | 2.79 (1.54–4.04) | 0 | 0.499 |
| Less than 9 | 11 | 863 | 0.62 (0.46–0.79) | 1.50 (0.96–2.04) | 71.8 | < 0.0001 |
OS: overall survival; DFS: disease-free survival; Random: Random effects; Fixed: Fixed effects; directly: HR was extracted directly
from the primary articles; indirectly: HR was extracted indirectly from the primary articles; CI: confidence interval
The association between linc00473 expression and TNM stage
10 appropriate articles comprising 748 patients try to examine the link between linc00473 level and TNM stage. The marked relationship was discovered between elevated linc00473 levels and higher TNM stage (OR: 3.78, 95%: 2.75–5.19, P < 0.0001) (Fig. 3). Although the heterogeneity is insignificant (I2 = 43, P = 0.07), the subgroup analysis per the diverse cancer type was also performed considering the different expression level of linc00473 in various cancer systems, and the significant positive association could also be uncovered in digestive system (OR: 4.50, 95%CI: 2.98–6.8, P < 0.0001), reproductive system (OR: 2.79, 95%CI: 1.04–7.48, P = 0.0004) and other system (OR: 16.00, 95%CI: 3.23–79.27, P = 0.0007) (Table 4).
Fig. 3.
Forest plot about the relationship between linc00473 expression and TNM stage and LNM in cancers. Review Manager 5.4.0 version was applied, OR with 95%CI were combined to evaluate the link between linc00473 level and cancer prognosis encompassing TNM. The marked relationship was discovered between elevated linc00473 levels and higher TNM stage (OR: 3.78, 95%: 2.75–5.19, P < 0.0001). Although the heterogeneity is insignificant (I2 = 43, P = 0.07), the subgroup analysis per the diverse cancer type was also performed considering the different expression level of linc00473 in various cancer systems, and the significant positive association could also be uncovered in digestive system (OR: 4.50, 95%CI: 2.98–6.8, P < 0.0001), reproductive system (OR: 2.79, 95%CI: 1.04–7.48, P = 0.0004) and other system (OR: 16.00, 95%CI: 3.23–79.27, P = 0.0007)
Table 4.
Pool effects of clinicopathologic characteristics in cancer patients with abnormal linc00473 expression
| Clinicopathologic characteristics | No. of studies | No. of patients | Odds ratio (95% CI) | Heterogeneity | ||
|---|---|---|---|---|---|---|
| Fixed | Random | I2(%) | P-value | |||
| Age | 11 | 801 | 0.96 (0.71–1.29) | 0.96 (0.71–1.30) | 0 | 0.9 |
| Gender | 7 | 443 | 0.74 (0.49–1.12) | 0.76 (0.46–1.25) | 25 | 0.35 |
| TNM (Ⅲ+Ⅳ vs. Ⅰ+Ⅱ) | 10 | 748 | 3.78 (2.75–5.19) | 4.12 (2.62–6.46) | 43 | 0.07 |
| Digestive system | 6 | 446 | 4.50 (2.98–6.8) | 4.49 (2.96–6.81) | 0 | 0.59 |
| Reproductive system | 3 | 262 | 2.36 (1.38–4.03) | 2.79 (1.04–7.48) | 59 | 0.09 |
| Other system | 1 | 40 | 16.00 (3.23–79.27) | 16.00 (3.23–79.27) | NA | NA |
| LNM (present vs. absent) | 8 | 638 | 2.16 (1.56–2.99) | 2.16 (0.97–4.80) | 80 | < 0.0001 |
| Digestive system | 5 | 376 | 2.24 (1.48–3.38) | 2.13 (0.59–7.64) | 87 | < 0.0001 |
| Non-digestive system | 3 | 262 | 2.03 (1.20–3.44) | 2.12 (0.85–5.27) | 64 | < 0.0001 |
| Tumor size | 7 | 490 | 3.10 (2.13–4.50) | 3.23 (2.07–5.03) | 24 | 0.24 |
| Digestive system | 4 | 228 | 4.11 (2.34–7.21) | 4.11 (2.33–7.26) | 0 | 0.55 |
| Non-digestive system | 3 | 262 | 2.47 (1.50–4.08) | 2.67 (1.26–5.64) | 51 | 0.13 |
| Histological grade | 6 | 498 | 1.85 (1.29–2.67) | 1.84 (1.25–2.70) | 7 | 0.37 |
| Digestive system | 5 | 376 | 1.95 (1.28–2.98) | 1.96 (1.18–3.26) | 23 | 0.27 |
| Non-digestive system | 1 | 122 | 1.59 (0.77–3.27) | 1.59 (0.77–3.27) | NA | NA |
| DM (present vs. absent) | 3 | 296 | 4.61 (2.53–8.39) | 4.11 (2.23–7.58) | 0 | 0.4 |
| Depth of invasion | 2 | 190 | 1.46 (0.83–2.58) | 1.78 (0.35–9.00.35.00) | 85 | 0.009 |
TNM: Tumor Node Metastasis, LNM: lymph node metastasis, DM: distant metastasis, CI: confidence interval, No.: number, NA: not applicable
The link between linc00473 level and LNM
8 enrolled publications assessed the link between linc00473 level and lymph node metastasis. The result of pooling OR and 95% CI revealed that heightened lin00473 level indicated easier lymph node metastasis in most cancers, but the result failed to reach statistically significant (OR: 2.16, 95%CI: 0.97–4.80, P = 0.06) (Fig. 4). Due to substantial heterogeneity among the 8 investigations, a cancer type-based subgroup analysis was performed, which demonstrated non-significant positive associations between elevated linc00473 expression and lymph node metastasis in both digestive system (OR: 2.13, 95%CI: 0.59–7.64, P = 0.25) and non-digestive system malignancies (OR: 2.12, 95%CI: 0.85–5.27, P = 0.10). More high-quality, large-sample relevant research was needed to support and improve the results of this study (Table 4).
Fig. 4.
Forest plot about the relationship between linc00473 expression and LNM in cancers
The link between linc00473 level and tumor size
7 research embracing 490 patients evaluated the link between linc00473 level and tumor size in diverse cancers. The analysis revealed that elevated linc00473 level was associated with larger tumor size in most cancers (OR: 3.10, 95%CI: 2.13–4.50, P < 0.00001) (Fig. 5). More detailed analysis also shows the same positive correlation between increasing linc00473 level and bigger tumor size in digestive system (OR: 4.11, 95%CI: 2.34–7.21, P < 0.00001) and non-digestive system (OR: 2.47 95%CI: 1.50–4.08, P = 0.0004) (Table 4).
Fig. 5.
Forest plot is about the relationship between linc00473 expression and Tumor size in cancers
The link between linc00473 level and other clinicopathologic parameters
We also explore the link between linc00473 level and other clinicopathologic factors, results show that increased linc00473 expression indicated poor histological grade (OR:1.85, 95%CI: 1.29–2.67, P = 0.0009) (Fig. 6A), easier distant metastasis (OR: 4.61, 95%CI: 2.53–8.39, P < 0.00001) (Fig. 6B). The insignificant correlation was also uncovered in depth of invasion (OR: 1.78, 95%CI: 0.35–9.00.35.00, P = 0.48) (Fig. 6C), age (OR: 0.96, 95%CI: 0.71–1.29, P > 0.05) and gender (OR: 0.74, 95%CI: 0.49–1.12, P > 0.05) (Table 4).
Fig. 6.
Forest plot about the relationship between linc00473 expression and Clinicopathological parameters in cancer. A Histological grade; B DM; C Depth of invasion
Sensitivity analysis and publication bias
The sensitivity analysis findings indicated that except for the results of two studies. The overall research results show strong stability and reliability (Fig. 7). Based on this, subgroup analysis was executed, and the findings revealed that after excluding the two studies, the overall results tended to be more stable (Supplementary Fig. 1). Based on the detailed analysis of the original research, we find that the author is inconsistent in the results of the literature pictures and the description of the results. The examination of Beeg’s statistical test indicated that the research findings demonstrated no significant publication bias (Fig. 8). The examination of Egger’s statistical test also indicated that the research findings demonstrated no significant publication bias (Fig. 9).
Fig. 7.
Leave-one-out analysis for linc00473 expression with overall survival (OS) in various cancers. HR: hazard ratio, CI: confidence interval
Fig. 8.
Funnel plot about the relationship between linc00473 expression and survival outcome in various cancers. A OS; B TNM stage; C LNM; D Tumor size; E Histological grade; F DM
Fig. 9.
Publication bias about the relationship between linc00473 expression and survival outcome in various cancers. A OS; B TNM stage; C LNM; D DM; E Tumor size; F Histological grade
Discussion
Linc00473 was first confirmed by Professor Timothy as notably upregulated in liver cancer in 2017 [34]. Subsequent studies have explored linc00473 levels in various tumor tissues. Research indicates elevated linc00473 levels in lung cancer, colorectal cancer, gastric cancer, osteosarcoma, breast cancer, esophageal cancer, glioma, etc. Numerous investigations have demonstrated that linc00473 enhances cellular proliferation, motility, invasiveness, and chemoresistance in cancer cells [18, 36], while decreased linc00473 expression substantially suppresses cancer development [37]. Mounting evidence demonstrated that increasing linc00473 expression predicts poor cancer prognosis, linc00473 is considered as a potential therapeutic target of cancer and a potential marker of cancer prognosis [38, 39].
A meta-analysis was executed to systematically assess the link between linc00473 level and clinical outcomes across different cancers. The analysis revealed that linc00473 serves as an unfavorable prognostic marker in cancer, with elevated linc00473 expression correlating to poorer cancer outcomes (HR: 1.850, 95%CI: 1.230–2.80). Due to substantial heterogeneity, stratified analyses were performed based on sample size, cancer type, follow-up duration, and HR extraction methods. Through detailed stratified analyses, we found that among different cancer types, heterogeneity was clearly localized to digestive system cancers (I² = 86%), as tumors of other systems exhibited no significant heterogeneity (I² = 0). This may be attributed to the findings of Wu HZ (2020), which showed that high expression of linc00473 predicts a favorable prognosis for colorectal cancer. Thus, the results and conclusions of this study can serve as a valuable reference. On the other hand, additional high-quality, large-sample studies with similar designs are needed to further support and enrich the findings of this research. The analyses consistently demonstrated the connection between elevated linc00473 expression and adverse cancer outcomes across multiple subgroups including respiratory system (HR: 2.23, 95%CI: 1.39–3.58), reproductive system (HR: 3.19, 95%CI: 2.00–5.11.00.11), other system (HR: 2.56, 95%CI: 1.37–4.80), the mean value cut-off subgroup (HR: 2.08, 95%CI: 1.43-2.73), NOS score 9 subgroup (HR: 2.79, 95%CI: 1.54–4.04), HR directly copy form primary study (HR: 1.84, 95%CI: 1.13–3.81) or HR was indirectly calculated based on survival curve and sample size (HR: 1.93, 95%CI: 1.20–2.66). Furthermore, analyses examined the link between linc00473 levels and additional prognostic parameters, encompassing TNM stage, lymph node metastasis, distant metastasis and tumor size. The findings indicated that elevated linc00473 expression correlates with advanced TNM stage, increased distant metastasis, larger tumor size and poor histological grade. Sensitivity analysis demonstrated minimal heterogeneity across individual studies, excluding 2 articles. It is suggested that all the results, except two articles, stably suggest that linc00473 is a reliable prognostic indicator of cancer. In short, increasing linc00473 may predict poor cancer prognosis. linc00473 represents a potential therapeutic target and prognostic biomarker. Existing studies have consistently demonstrated that linc00473 promotes lymph node metastasis in most cancer types—for instance, by activating the epithelial-mesenchymal transition (EMT) pathway (to enhance cell invasiveness), upregulating matrix metalloproteinase (MMP) expression (to degrade extracellular matrix and facilitate cell migration), or interacting with downstream oncogenic RNAs/proteins to strengthen metastatic capabilities. However, emerging preliminary evidence suggests a potential cancer-type-specific effect: linc00473 may exert an inhibitory role in LNM of cholangiocarcinoma. This tissue-specific regulatory pattern (promoting LNM in most cancers vs. potentially inhibiting it in cholangiocarcinoma) is likely a key driver of the observed high subgroup heterogeneity, as conflicting regulatory effects across cancer types would dilute or distort the overall association in the pooled analysis.
Several studies investigated the biological mechanism between linc00473 and bad cancer at the molecular level (Fig. 10 and Table 5). Chen et al. suggested that linc00473 could function as competitive endogenous RNA, increasing Spindlin1 (SPIN1) expression by sponging miR-374a-5p, promoting resistance of ESCC cells to radiotherapy [25]. Niu et al. determined that linc00473 contributed to breast cancer cell proliferation, invasion and migration by functioning as competitive endogenous RNA, elevating Mitogen-Activated Protein Kinase 1 (MAPK1) levels through miR-198 sponging [28]. Bai et al. displayed that linc00473 promotes cell proliferation and migration and inhibits cell apoptosis of breast cancer via down-regulating miR-497 expression [29]. Hao et al. suggested that linc00473 can promote cell proliferation and migration of pancreatic cancer by activating cAMP to activate phosphorylation of β-catenin [33]. Han et al. revealed that linc00473 enhanced radioresistance, stimulated cell proliferation, and suppressed apoptosis in head and neck squamous cell carcinoma (HNSCC) cells through Wnt/β-catenin pathway activation [34]. Huang et al. indicated that linc00473 was up-regulated in Cholangiocarcinoma (CCA), high linc00473 expression may drive the growth and migration of CCA via up-regulating DDX5 expression via sponging miR-506 [17]. Zhuo et al. reported that linc00473 acting as ceRNA, inducing the proliferation and migration of gastric cancer cells through up-regulating cyclin D2 expression by down-regulating miR-16-5p [14]. Shi et al. suggested that linc00473 may promote the proliferation, invasion and migration of cervical cancer via interacting with interleukin enhancer binding factor 2 (ILF2) and inhibits ILF2 degradation [15]. Chen et al. suggested that linc00473 could augment HCC cell proliferation, invasion and induced epithelial emesenchymal transition (EMT) process by upregulating survivin expression [30]. Liu et al. demonstrated that linc00473 promotes the radioresistance of ESCC cells via sponging miR-497-5p and contributing to the cell division cycle 25 A (CDC25A) expression [26]. Wang et al. suggested that linc00473 enhanced glioma cell proliferation, migration, and invasion via miR-195-5p sponging and YAP1-TEAD1-Hippo signaling interaction [32]. Zhang et al. discovered that linc00473 operated as ceRNA, facilitating glioma cell proliferation and invasion by increasing cyclin-dependent kinases 6 (CDK6) through miR-637 binding and suppression [40]. Qin et al. suggested that linc00473 promotes the radioresistance of NSCLC cells via competitive sponging miR-513a-3p [22]. Xu et al. uncovered that linc00473 promoted NSCLC cell proliferation, migration, invasion, and apoptosis suppression through miR-4975p sponging and downregulation [27].
Fig. 10.
linc00473 involved a serious of cellular biological role in cancers
Table 5.
Transition of cell phenotype and related molecular mechanisms with abnormal SNHG expression in gastric cancers
| Author and Years | cncer type | Level of expression | MicroRNA | Gene or pathway | Function |
|---|---|---|---|---|---|
| Chen 2018 | ESCC | Upregulated | miR-374a-5p | SPIN1 | Promoting resistance to radiotherapy |
| Niu 2019 | BC | Upregulated | miR-198 | MAPK1 | Promote proliferation, invasion and migration |
| Bai 2019 | BC | Upregulated | miR-497 | – | Promote proliferation and migration, inhibit apoptosis |
| Hao 2020 | PC | Upregulated | – | cAMP/β-catenin | Promote cell proliferation and migration |
| Han 2018 | HNSCC | Upregulated | – | Wnt/β-catenin | Induce radioresistance, promote cell proliferation and inhibit apoptosis |
| Huang 2020 | CCA | Upregulated | miR-506 | DDX5 | Drive proliferation and migration |
| Zhou 2021 | GC | Upregulated | miR-16-5p | CCND2 | Inducing the proliferation and migration |
| Shi 2017 | CC | Upregulated | miR-34a | ILF2 | Promote the proliferation, invasion and migration |
| Chen 2018 | HCC | Upregulated | – | Survivin | Enhances cell proliferation, invasion and EMT process |
| Liu 2020 | ESCC | Upregulated | miR-497-5p | CDC25A | Contributes to the radioresistance |
| Wang 2020 | Glioma | Upregulated | miR-195-5p | YAP1-TEAD1-Hippo signaling | Contributes to the proliferation, migration and invasion |
| Zhang 2020 | Glioma | Upregulated | miR-637 | CDK6 | Inducing the proliferation and invasion |
| Wu 2020 | CRC | Upregulated | miR-574, miR-15b | APAF1 | Contributes to the proliferation and invasion, inhibit the apoptosis |
| Xu 2021 | NSCLC | Upregulated | miR-497-5p | ERK/p38 and MAPK signalling pathways | Promotes proliferation, migration, invasion and inhibition of apoptosis |
| Qin 2020 | NSCLC | Upregulated | miR-513a-3p | – | Promotes radioresistance |
| Zhang 2018 | GC | Upregulated | – | MMP2, MMP9 | Promote migration and invasion |
SPIN1: Spindlin1, MAPK1: Mitogen-Activated Protein Kinase 1, HNSCC: head and neck squamous cell carcinoma, CCA: Cholangiocarcinoma, GC: gastric cancer, CCND2: cyclin D2, ILF2: interleukin enhancer binding factor 2, CC: cervical cancer, HCC: Hepatocellular carcinoma, ESCC: esophageal squamous cell carcinoma, CDC25A: cell division cycle 25 A, YAP1: Yes-associated protein 1, TEAD1: TEA domain family member 1, CDK6: cyclin-dependent kinases 6, CRC: clorectal cancer, APAF1: apoptotic protease-activating factor 1, MMP2: matrix metalloproteinase 2, MMP9: matrix metalloproteinase 9, GC: gastric cancer. ERK: extracellular regulated protein kinases, NSCLC: non-small cell lung cancer, PC: Pancreatic cancer, BC: breast cancer
This meta-analysis inevitably exists some limitations, first, not all HR values and 95% confidence intervals are calculated through SPSS software, but some HR values are obtained through the Engauge software, which makes the HR values between different studies statistically biased. Second, the study population exclusively comprised Asian patients, which makes the results of this study more suitable for representing the Asian population, not the world population, while no geographical restrictions were imposed during study selection, all included cohorts were retrospectively derived from Chinese medical centers. This emergent pattern highlights regional research trends rather than methodological bias, and future worldwide research validation studies would be valuable. Third, inevitable publication bias. For instance, studies showing positive outcomes tend to receive publication preference compared to those with negative findings, potentially influencing the ultimate analysis outcomes. Fourth, the included study only reported OS and failed to observe the relationship between other survival outcomes and lncRNAs. It is worth noting that the Wang X 2020 study had a small sample size of cases, which may contributed to the relatively large fluctuations in its reported results; alternatively, high expression of linc00473 might be more strongly predictive of poor prognosis specifically in gliomas. However, when considering cancers in general, the association between linc00473 and prognosis is less pronounced for some cancer types. Finally, various studies have different criteria for the definition of high expression of linc00473, which may be a factor contributing to the heterogeneity of study merger. However, compared with published relevant studies, this study, based on subgroup analysis, thoroughly explored the sources of heterogeneity in overall survival, including patient numbers, follow-up time, cut-off points, NOS scores, and analysis methods. Also, this study, based on subgroup analysis, explored the sources of heterogeneity influencing TNM staging and LNM.
Conclusion
Linc00473 was reported up-regulated in various tumor tissues including NSCLC, breast cancer, cervical cancer etc. High linc00473 expression indicated poor cancer survival outcome, advanced TNM stage, bigger tumor size, earlier distant metastasis of tumor cell. Linc00473 potentially functions as a potential therapeutic target.
Supplementary Information
Acknowledgements
Not applicable.
Author contributions
Ze He and Wang Chen design the project; Pengge Wang and Tiewei Sun searched databases and performed literature screen; Wang Chen and Tiewei Sun extracted and analyzed the data, analysis; Ze He and Wang Chen organized the images in the manuscript; Pengge Wang, Tiewei Sun, Ze He and Wang Chen contributed to writing the manuscript. Final draft was approved by all the authors.
Funding
Not applicable.
Data availability
All experimental information and analytical results obtained throughout this investigation are presented within this publication or can be accessed by contacting the corresponding author with appropriate justification.
Declarations
Ethics approval and consent to participate
This research does not involve any clinical patient investigation; thus, no ethical approval was necessary. The authors take full responsibility for guaranteeing that any concerns regarding the precision and completeness of each component of this work has been thoroughly examined and addressed.
Consent for publication
Not Applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
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References
- 1.Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229–63. [DOI] [PubMed] [Google Scholar]
- 2.Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, et al. Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 2012;62(4):220–41. [DOI] [PubMed] [Google Scholar]
- 3.Xia C, Dong X, Li H, Cao M, Sun D, He S, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J. 2022;135(5):584–90. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Friman TK, Jäämaa-Holmberg S, Åberg F, Helanterä I, Halme M, Pentikäinen MO, et al. Cancer risk and mortality after solid organ transplantation: a population-based 30-year cohort study in Finland. Int J Cancer. 2022;150(11):1779–91. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–32. [DOI] [PubMed] [Google Scholar]
- 6.Goodall GJ, Wickramasinghe VO. RNA in cancer. Nat Rev Cancer. 2021;21(1):22–36. [DOI] [PubMed] [Google Scholar]
- 7.Statello L, Guo CJ, Chen LL, Huarte M. Gene regulation by long non-coding RNAs and its biological functions. Nat Rev Mol Cell Biol. 2021;22(2):96–118. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Peng WX, Koirala P, Mo YY. LncRNA-mediated regulation of cell signaling in cancer. Oncogene. 2017;36(41):5661–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Schmitt AM, Chang HY. Long noncoding RNAs in cancer pathways. Cancer Cell. 2016;29(4):452–63. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Schmitz SU, Grote P, Herrmann BG. Mechanisms of long noncoding RNA function in development and disease. Cell Mol Life Sci. 2016;73(13):2491–509. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Zhu Y, Li B, Liu Z, Jiang L, Wang G, Lv M, et al. Up-regulation of LncRNA SNHG1 indicates poor prognosis and promotes cell proliferation and metastasis of colorectal cancer by activation of the Wnt/β-catenin signaling pathway. Oncotarget. 2017;8(67):111715–27. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Lan T, Yan X, Li Z, Xu X, Mao Q, Ma W, et al. Long non-coding RNA PVT1 serves as a competing endogenous RNA for miR-186-5p to promote the tumorigenesis and metastasis of hepatocellular carcinoma. Tumor Biol. 2017;39(6):1010428317705338. [DOI] [PubMed] [Google Scholar]
- 13.Dinh TA, Vitucci EC, Wauthier E, Graham RP, Pitman WA, Oikawa T, et al. Comprehensive analysis of the cancer genome atlas reveals a unique gene and non-coding RNA signature of fibrolamellar carcinoma. Sci Rep. 2017;7:44653. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Zhuo S, Sun M, Bai R, Lu D, Di S, Ma T, et al. Long intergenic non-coding RNA 00473 promotes proliferation and migration of gastric cancer via the miR-16-5p/CCND2 axis and by regulating AQP3. Cell Death Dis. 2021;12(5):496. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Shi C, Yang Y, Yu J, Meng F, Zhang T, Gao Y. The long noncoding RNA LINC00473, a target of MicroRNA 34a, promotes tumorigenesis by inhibiting ILF2 degradation in cervical cancer. Am J Cancer Res. 2017;7(11):2157–68. [PMC free article] [PubMed] [Google Scholar]
- 16.Song Q, Zhang H, He J, Kong H, Tao R, Huang Y, et al. Long non-coding RNA LINC00473 acts as a microRNA-29a-3p sponge to promote hepatocellular carcinoma development by activating Robo1-dependent PI3K/AKT/mTOR signaling pathway. Ther Adv Med Oncol. 2020;12:1758835920937890. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Huang L, Jiang X, Li Z, Li J, Lin X, Hu Z, et al. Linc00473 potentiates cholangiocarcinoma progression by modulation of DDX5 expression via miR-506 regulation. Cancer Cell Int. 2020;20:324. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Li L, Zhang X, Liu N, Chen X, Peng C. LINC00473: a novel oncogenic long noncoding RNA in human cancers. J Cell Physiol. 2021;236(6):4174–83. [DOI] [PubMed] [Google Scholar]
- 19.Ruiz-Bañobre J, Rodriguez-Casanova A, Costa-Fraga N, Bao-Caamano A, Alvarez-Castro A, Carreras-Presas M, et al. Noninvasive early detection of colorectal cancer by hypermethylation of the LINC00473 promoter in plasma cell-free DNA. Clin Epigenetics. 2022;14(1):86. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Zhang C, Yang T. Long non-coding RNA LINC00473 promotes breast cancer progression via miR-424-5p/CCNE1 pathway. Protein Peptide Lett. 2023;30(1):72–84. [DOI] [PubMed] [Google Scholar]
- 21.Mo J, Li B, Zhou Y, Xu Y, Jiang H, Cheng X, et al. LINC00473 promotes hepatocellular carcinoma progression via acting as a CeRNA for microRNA-195 and increasing HMGA2 expression. Biomed Pharmacother. 2019;120:109403. [DOI] [PubMed] [Google Scholar]
- 22.Qin P, Li Y, Liu J, Wang N. Knockdown of LINC00473 promotes radiosensitivity of non-small cell lung cancer cells via sponging miR-513a-3p. Free Radic Res. 2020;54(10):756–64. [DOI] [PubMed] [Google Scholar]
- 23.Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;8:16. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–5. [DOI] [PubMed] [Google Scholar]
- 25.Chen W, Zhang Y, Wang H, Pan T, Zhang Y, Li C. LINC00473/miR-374a-5p regulates esophageal squamous cell carcinoma via targeting SPIN1 to weaken the effect of radiotherapy. J Cell Biochem. 2019;120(9):14562–72. [DOI] [PubMed] [Google Scholar]
- 26.Liu WH, Qiao HY, Xu J, Wang WQ, Wu YL, Wu X. LINC00473 contributes to the radioresistance of esophageal squamous cell carcinoma by regulating microRNA–497–5p and cell division cycle 25A. Int J Mol Med. 2020;46(2):571–82. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Xu SH, Bo YH, Ma HC, Zhang HN, Shao MJ. LncRNA LINC00473 promotes proliferation, migration, invasion and inhibition of apoptosis of non-small cell lung cancer cells by acting as a sponge of miR-497-5p. Oncol Lett. 2021;21(6):429. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Niu L, Zhou Y, Zhang W, Ren Y. Long noncoding RNA LINC00473 functions as a competing endogenous RNA to regulate MAPK1 expression by sponging miR-198 in breast cancer. Pathol Res Pract. 2019;215(8):152470. [DOI] [PubMed] [Google Scholar]
- 29.Bai J, Zhao WY, Li WJ, Ying ZW, Jiang DQ. Long noncoding RNA LINC00473 indicates a poor prognosis of breast cancer and accelerates tumor carcinogenesis by competing endogenous sponging miR-497. Eur Rev Med Pharmacol Sci. 2019;23(8):3410–20. [DOI] [PubMed] [Google Scholar]
- 30.Chen H, Yang F, Li X, Gong ZJ, Wang LW. Long noncoding RNA LNC473 inhibits the ubiquitination of survivin via association with USP9X and enhances cell proliferation and invasion in hepatocellular carcinoma cells. Biochem Biophys Res Commun. 2018;499(3):702–10. [DOI] [PubMed] [Google Scholar]
- 31.Wu H, Hu X, Li Y, Chen Q, Sun T, Qiao Y, et al. LNC473 regulating APAF1 IRES-dependent translation via competitive sponging miR574 and miR15b: implications in colorectal cancer. Mol Ther Nucleic Acids. 2020;21:764–79. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Wang X, Li XD, Fu Z, Zhou Y, Huang X, Jiang X. Long non–coding RNA LINC00473/miR–195–5p promotes glioma progression via YAP1–TEAD1–Hippo signaling. Int J Oncol. 2020;56(2):508–21. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Hao XF, Zhang YX, Wang XX, Sun W, Zhao J, Chen GR. LINC00473 functions as an oncogene and predicts poor prognosis in pancreatic cancer via the cAMP/β-catenin axis. Eur Rev Med Pharmacol Sci. 2020;24(10):5345–52. [DOI] [PubMed] [Google Scholar]
- 34.Han PB, Ji XJ, Zhang M, Gao LY. Upregulation of LncRNA LINC00473 promotes radioresistance of HNSCC cells through activating Wnt/β-catenin signaling pathway. Eur Rev Med Pharmacol Sci. 2018;22(21):7305–13. [DOI] [PubMed] [Google Scholar]
- 35.Zhang W, Song Y. LINC00473 predicts poor prognosis and regulates cell migration and invasion in gastric cancer. Biomed Pharmacother. 2018;107:1–6. [DOI] [PubMed] [Google Scholar]
- 36.Ghafouri-Fard S, Hussen BM, Mohaqiq M, Shoorei H, Baniahmad A, Taheri M, et al. Interplay between non-coding RNAs and programmed cell death proteins. Front Oncol. 2022;12:808475. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Zhu S, Fu W, Zhang L, Fu K, Hu J, Jia W, et al. LINC00473 antagonizes the tumour suppressor miR-195 to mediate the pathogenesis of Wilms tumour via IKKα. Cell Prolif. 2018. 10.1111/cpr.12416. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Ghafouri-Fard S, Abak A, Hussen BM, Taheri M, Sharifi G. The emerging role of non-coding RNAs in pituitary gland tumors and meningioma. Cancers. 2021. 10.3390/cancers13235987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Xing Z, Li S, Liu Z, Zhang C, Meng M, Bai Z. The long non-coding RNA LINC00473 contributes to cell proliferation via JAK-STAT3 signaling pathway by regulating miR-195-5p/SEPT2 axis in prostate cancer. Biosci Rep. 2020. 10.1042/BSR20191850. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40.Zhang Q, Wang G, Xu L, Yao Z, Song L. Long non-coding RNA LINC00473 promotes glioma cells proliferation and invasion by impairing miR-637/CDK6 axis. Artif Cells Nanomed Biotechnol. 2019;47(1):3896–903. [DOI] [PubMed] [Google Scholar]
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Data Availability Statement
All experimental information and analytical results obtained throughout this investigation are presented within this publication or can be accessed by contacting the corresponding author with appropriate justification.