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. 2017 Dec 10;51(1):e12422. doi: 10.1111/cpr.12422

Long non‐coding PANDAR as a novel biomarker in human cancer: A systematic review

Yifan Zou 1,2,†, Yuantang Zhong 1,†, Junjie Wu 2,†, Huizhong Xiao 1,†, Xintao Zhang 1, Xinhui Liao 1, Jianfa Li 3, Xuhua Mao 1, Yuchen Liu 1,✉, Fuyou Zhang 1,✉
PMCID: PMC6528858  PMID: 29226461

Abstract

Objectives

Long non‐coding RNAs (lncRNAs) are characterized as a group of RNAs that more than 200 nucleotides in length and have no protein‐coding function. More and more evidences provided that lncRNAs serve as key molecules in the development of cancer. Deregulation of lncRNAs functions as either oncogenes or tumour suppressor genes in various diseases. Recently, increasing studies about PANDAR in cancer progression were reported. In our review, we will focus on the current research on the character of PANDAR include the clinical management, tumour progression and molecular mechanisms in human cancers.

Materials and methods

We summarize and analyze current studies concerning the biological functions and mechanisms of lncRNA PANDA in tumour development. The related studies were obtained through a systematic search of Pubmed.

Results

PANDAR was a well‐characterized oncogenic lncRNA and widely overexpressed in many tumours. PANDAR is upregulated in many types of cancer, including colorectal cancer, lung cancer, renal cell carcinoma, cholangiocarcinoma, osteosarcoma, thyroid cancer and other cancers. Upregulation of PANDAR was significantly associated with advanced tumour weights, TNM stage and overall survival. Furthermore, repressed of PANDAR would restrain proliferation, migration and invasion.

Conclusion

PANDAR may act as a powerful tumour biomarker for cancer diagnosis and treatment.

Keywords: diagnostic biomarker, long non‐coding RNA, PANDAR, therapeutic target

1. INTRODUCTION

Cancer is considered as one of the leading causes of death worldwide owing to delay diagnosis, poor prognosis and high rate of recurrence. Recent study showed that 1 688 780 new cancer cases and 600 920 cancer deaths occur in the United States during 2017.1 What was worse, these numbers are growing constantly due to lack of effective therapy for cancer.2 Therefore, further research should be launched to detect new therapeutic biomarker for cancer treatment.

Approximately 70% of human genome is transcribed into RNA, however, only less than 2% of the human genome codes for protein.3, 4 Recent study showed non‐coding RNAs (ncRNAs) are transcribed from non‐protein‐coding DNA sequences and key regulatory RNAs.5 Long non‐coding RNAs (LncRNAs) belong to ncRNAs that are longer than 200 nucleotides in length.6 Previous studies suggested that the lncRNAs acted as transcriptional modulator, splicing regulator, post‐transcriptional processor, enhancer, molecular decoys for miRNAs, chromatin remodeler, a guide for protein‐protein, protein‐DNA and protein‐RNA interactions.7, 8 For instance, H19 was one of the first reported long non‐coding RNAs. It was enhanced in breast, urological, respiratory and brain tumours. H19 could function in trans to suppress the levels of a number of imprinted genes in the hypothesized Imprinted Gene Network (IGN) including Igf2r and.9, 10 LncRNA HOX antisense intergenic RNA(HOTAIR) was upregulated in breast cancer, gastric cancer and hepatocellular carcinoma.11, 12, 13 HOTAIR causes the transcriptional suppressing of the HOXD locus on chromosome 2 in trans.14 It recruits polycomb repressiving complex 2 (PRC2) and regulates the chromosome occupancy of EZH2 (a subunit of PRC2), which causes histone H3 lysine 27 trimethylation of the HOXD locus.

Accumulating evidence indicates that lncRNAs are frequently deregulated in many kinds of cancer, playing critical roles in tumourigenesis. According to the function of lncRNAs in diverse cancer types, they can be classified into tumour suppressors or oncogenes.15, 16 MEG3 and GAS5 are famous tumour suppressor lncRNAs.17, 18, 19 HOTAIR, MALAT‐1, ATB, SPRY4‐IT1 and CCAT2 are well‐known oncogenic lncRNAs, which can induce tumourigenesis.16, 20, 21, 22, 23 LncRNAs take part in various aspects of cell biology and not doubt that contribute to tumour development potentially through stimulating or inhibiting cell proliferation, apoptosis, differentiation, invasion and metastasis.24 Dysregulation of lncRNAs leads to tumour formation, contributing to cancer development, progression and metastasis.

In recent years, more and more evidences demonstrated the tissue‐specific expression of P21‐associated ncRNA DNA damage activated (PANDAR) in many human cancers. Dysregulation of PANDAR is correlated with the progression of cancers, affecting the tumour size, clinical stage and TNM stage of cancer patients. Importantly, PANDAR is responsible for proliferation, migration, invasion and apoptosis of cancer cells. PANDAR has been highlighted as potential diagnostic and therapeutic tools in malignancies. In this paper, we will debate the latest knowledge about the effects and underlying mechanisms of PANDAR in various cancers’ progression (Table 1).

Table 1.

BANCR in human cancer

Cancer types Cell lines Associations Related genes and protein References
Colorectal cancer SW480, SW620, HCT116, DLD‐1, HT‐29, LOVO Local invasion, lymph node metastasis, TNM stage, overall survival, cycle progression, proliferation, invasion, apoptosis Bcl‐2, BaxE‐cadherin, N‐cadherin, vimentin, β‐catenin, Snail, Twist, PUMA 28, 29, 32
Lung cancer NCI‐H1299, A549, SPC‐A1, SK‐MES‐1 Tumour size, TNM stag invasion, apoptosis P53, Bcl‐2, NF‐YA 37, 38
Renal cell carcinoma 7860, Caki‐1 Advanced tumour weights, TNM stage, overall survival, cell cycle proliferation, invasion, apoptosis P21, cyclin D1, cyclin E1, CDK4, Bcl‐2, Bax, Mcl‐1, PI3K/Akt/mTOR pathway, caspase‐3, PARP,MMP2 44, 45
Breast cancer BT474, SK‐BR3, MCF‐7, T47D, MDA‐MB‐231, MCF‐10A, 76n, HMLE Tumour growth, cells cycle proliferation P16, Bmi1 51
Cholangiocarcinoma KMBC, HCCC‐9810, HuCCT1, CCLP‐1, Huh‐28, QBC939,RBE Lymph node invasion, TNM stage, post‐operative relapse proliferation, invasion, apoptosis Caspase‐3, caspase‐9 Bcl‐2, BaxN‐cadherin, Vimentin, E‐cadherin. 56
Osteosarcoma U2OS Cell cycle P18 60
Thyroid Cancer K1, TPC‐1, SW579, FTC133, XTC‐ Cells cycle proliferation, invasion, apoptosis Bcl‐2, Baxcyclin D1, Chk1, Cdc25A. 64
Hepatocellular carcinoma HCCLM3, Hep3B, HepG2, Huh‐7, MHCC97H, PLC, SMMC‐7402, SMMC‐7721, LO2 Liver cirrhosis, HBsAg, AFP, tumour nodule, vascular invasion, TNM stage, poorer survival, shorter recurrence, proliferation 65
Gastric cancer Depth of invasion, TNM stage, lymphatic metastasis 66
Bladder cancer 5637, SW780, UMUC3, T24, SVHUC‐1 Higher histological grade, advanced TNM stage proliferation, apoptosis 67
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2. PANDAR IN VARIOUS CANCERS

2.1. Colorectal cancer

Colorectal cancer (CRC) is the third most famous cancer in the world, which becomes the fourth most usual cause of cancer‐related deaths.25 Cancer metastasis is the major reason for high mortality of CRC patients.26 Despite improvements in surgical and adjuvant chemotherapies for CRC treatments, cancer relapse and metastasis are still inevitable.27 Lack of effective tumour biomarkers for tumour progression and metastasis is responsible for the failure of CRC therapy. Thus, it is necessary to detect the pathogenesis of CRC to find out novel treatments and valuable biomarkers.

Lu et al28 discovered that the expression of PANDAR was higher in colorectal cancer tissues compared with adjacent tissues. Furthermore, Li et al29 found that the levels of PANDAR were meaningfully related to invasion, lymph node metastasis and TNM stage. Patients who with higher expression levels of PANDAR showed poorer overall survival than those lower expression group. Multivariate Cox regression analysis suggested that PANDAR was likely to become an independent prognostic role of CRC patients.

Importantly, knockdown of PANDAR meaningfully restrained cell proliferation, cycle progression, migration and invasion of colorectal cancer cell. Li et al29 firstly investigated the role of PANDAR in the CRC cell cycle. Knockdown of PANDAR displayed CRC cell lines were arrested at G0/G1 phase, but reduced at the S phase population. Next, the authors investigated the levels of Bcl‐2 and Bax in CRC cell lines after knockdown of PANDAR. In addition, Bcl‐2 resistant various apoptosis‐inducing factors in various cancer. Bax is one of homologous gene from Bcl‐2 family, forming a heterodimer with Bcl‐2 to suppress anti‐apoptotic impact.30 Experiment results indicated that knockdown of PANDAR inhibited the levels of Bcl‐2 and reinforced the levels of Bax. In other hand, previous studies suggested that epithelial mesenchymal transition (EMT) was one of important mechanism in cell migration and invasion.31 When PANDAR was knockdowned in colorectal cancer cell lines, the levels of N‐cadherin, vimentin, β‐catenin, Snail and Twist were observably inhibited, but the levels of E‐cadherin were meaningfully enhanced. Above results suggested that the underlying mechanisms of PANDAR may be carried out by regulating Bcl‐2 family and EMT pathway28 (Figure 1).

Figure 1.

Figure 1

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Knockdown of PANDAR‐induced cell cycle arrest at the G0/G1 phase. Knockdown of PANDAR‐boosted cell apoptosis via downregulated the levels of Bcl‐2 and upregulated Bax. Downregulation of PANDAR‐inhibited cell invasion via upregulated the levels of E‐cadherin and decreased expression of N‐cadherin, vimentin, β‐catenin, Snail and Twist

However, Chen et al32 put forward different idea. The authors found that the levels of expression in CRC cell lines are consistent with adjacent tissues. Furthermore, there was no clearly different proliferation ability in CRC cell lines. Knockdown of PANDAR showed little effects on the apoptosis and senescence of CRC cell lines. However, curcumin has already been proved to suppress colon carcinogenesis and progression of CRC.33 Knockdown of PANDAR enhanced cell senescence and led to increased P53 upregulated modulator of apoptosis (PUMA) expression levels in curcumin‐treated CRC cells. In addition, PUMA, one of pro‐apoptotic genes, can enhance apoptotic response in many kinds of human tumour.34 In summary, above results indicated that curcumin induced CRC cells apoptosis by knockdown of PANDAR partly via stimulation of PUMA expression.

2.2. Lung cancer

Lung cancer is the most frequent cause of cancer‐related death worldwide.35 Approximately 80‐85% of lung cancer patients are diagnosed with non‐small cell lung cancer (NSCLC).36 Despite of advances in exanimation and new therapies for lung cancer, prognosis of NSCLC remains unsatisfied, and metastasis and recurrence are the main causes for poor prognosis. However, vast majority of NSCLC patients unfortunately are diagnosed at an advanced stage. Therefore, it is necessary to disclose the molecular mechanisms of NSCLC to diagnose and develop effective therapies.

The levels of PANDAR were meaningfully correlated to NSCLC. Han et al37 found the expression of PANDAR was generally decreased both in NSCLC tissues and cell lines, coincide with greater tumour weight and higher grade of TNM stage. Furthermore, statistical analysis showed that the levels of PANDAR were a meaningfully independent indicator for poorer survival group. Similarity, Zhang et al38 suggested that PANDAR was involved in the process of NSCLC. Two years of follow‐up the disease‐free survival time (DFS) demonstrated that PANDAR was poor prognostic factor.

More than 50% cancer cases were accompanied with P53 mutations or absence. Han et al37 confirmed that enhanced the levels of P53 would upregulate the levels of PANDAR. The authors suspected that it might induce the suppressed of PANDAR in some extent in NSCLC. Furthermore, the transcription factor NF‐YA‐binding site is the essential promoter of cell apoptosis genes at the downstream of P53.39 The Bcl‐2 protein family positively correlate with cell apoptosis and the level of Bcl‐2 is usually increased in various cancer.40 Upregulation of PANDAR would repress the levels of Bcl‐2 in NSCLC cell lines. Downregulation of NF‐YA would restrain the levels of Bcl‐2. In addition, overexpression of PANDAR showed the decreased NF‐YA binding at the promoter of Bcl‐2. These data revealed that Bcl‐2 might be the key of PANDAR/NF‐YA‐regulated genes. In a word, Bcl‐2 enhances tumour proliferation and restrains apoptosis in a way because of downregulation of PANDAR by releasing NF‐YA and inducing P53. In summary, PANDAR may show as a new therapeutic biomarker in the future. (Figure 2).

Figure 2.

Figure 2

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Bcl‐2 boosts tumour cell proliferation and inhibits apoptosis in part due to the downregulation of lncRNA PANDAR, which releases the NF‐YA and induces the downregulation of P53

2.3. Renal cell carcinoma

Renal cell carcinoma (RCC) contributes to about 3% of all human cancer, which on behalf of the most fatal urological cancer with nearly 202 000 cases and 102 000 deaths worldwide.41 The incidence of RCC has sharply increased for over 20 years,42 and generally patients are asymptomatic and non‐palpable in early stages. Currently, surgery represents the most important therapeutic option for RCC management, but nephrectomy of the primary tumour is curative only if the tumour is still localized in the kidney.43 Therefore, significant biomarker for effectively detection and therapeutic of RCC are absolutely necessary.

Xu et al44 found that PANDAR was meaningfully increased compared with adjacent tissue both in RCC tissues and cell lines. Moreover, higher levels of PANDAR were specifically related to advanced tumour weights, TNM stage and overall survival. Importantly, Wu et al45 collected the serum samples from 71 RCC patients which indicated that PANDAR was an indicator of the RCC diagnosis.

Xu et al44 disclosed that overexpression of PANDAR can enhance cell proliferation and invasion and restrain cell apoptosis in many pathways. In addition, MMPs (Matrix metalloproteinases) have a key role in cell invasion and migration,46 regulating the metabolism of extracellular matrix involves many tumour progression.47 Knockdown of PANDAR showed the levels of MMP2 were meaningfully downregulated. In other words, PANDAR was likely to enhance cell invasion by downregulating the levels of MMP‐2.

Knockdown of PANDAR‐induced RCC cell cycle arrested at the G0/G1 phase, oppositely, decreased at the S phase. Further experimental showed that the levels of cyclin E1, CDK4 and cyclin D1were dramatically decreased, oppositely, P21 was markedly increased when PANDAR was silenced. In conclusion, knockdown of PANDAR might regulate the Cyclin‐CDKs signal pathway inducing cell cycle arrested at the G0/G1 phase partly.

Moreover, caspase‐3 and PARP, kinds of apoptosis‐associated proteins, were detected cleaved after downregulation of PANDAR. In addition, Bcl‐2 family proteins were associated with cell apoptosis closely in various cancers. Silenced PANDAR showed the levels of Mcl‐1 and Bcl‐2 were decreased, oppositely, Bax was increased. Previous studies disclosed PI3K/Akt/mTOR pathway took part in cell proliferation and apoptosis in many human tumours.48The authors revealed that knockdown of PANDAR decreased the levels of mTOR and the phosphorylation of PI3K and Akt. Taken together, the authors disclosed that PANDAR‐induced RCC cell apoptosis by regulating Bcl‐2 family proteins and PI3K/Akt/mTOR pathway. In summary, PANDAR may be a novel therapeutic biomarker for RCC patients in the future (Figure 3).

Figure 3.

Figure 3

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Knockdown of PANDAR‐induced cell cycle arrest at the G0/G1 phase via upregulated P21 and downregulated the expression of cyclin D1, cyclin E1 and CDK4. Knockdown of PANDAR‐boosted cell apoptosis via downregulated the levels of Bcl‐2, Mcl‐1, PI3K/Akt/mTOR pathway, caspase‐3, PARP and upregulated Bax. Knockdown of PANDAR‐inhibited cell invasion via upregulated the levels of MMP2

2.4. Breast cancer

Breast cancer usually comes from mammary gland epithelial tissue, which is the most famous cancer and the most frequent cause of cancer death among women universally.49 It was estimated that about 1.67 million new cases of breast cancer were diagnosed in 2012 contributing to 25% of all cancers, while 522 000 died from the disease.50 It is a very complex process that the progression of breast cancer is linked with many signalling pathways. Therefore, a better understanding of molecular pathways in breast cancer can detect the disease at an early stage and provide potential therapies.

Song et al51 found the expression of PANDAR was increased both in breast cancer tissue and cell lines. To investigate the effects of PANDAR, the authors silenced PANDAR and detected a meaningfully inhibited cell growth. Moreover, they examined the levels of PANDAR in breast cancer cells cycle. The levels of PANDAR increased from G1 to S phase. It had no obvious change at G2, M and G1 phases. Contrarily, knockdown of PANDAR repressed G1 to S transition. Furthermore, they explored potential signalling pathway regulated by PANDAR. The result showed that downregulation of PANDAR could enhance the levels of P16. Moreover, co‐transfection with P16 could reverse the increase of G1 phase ration by knockdown of PANDAR partly. In a word, it suggested that PANDAR might enhance the G1 to S transition by decreasing the levels of P16. Previously studies revealed that the levels Bmi1 were boosted in various human tumour, related to cancer clinical stage and poor prognosis.52 It could directly inhibit the expression of P16.53 PANDAR was upregulated by silencing Bmi1. Experiment results indicated silence of PANDAR‐induced downregulation of Bmi1 binding at the promoter of P16. In summary, it suggested that PANDAR might be a significant biomarker regulating the progression of breast cancer.

2.5. Cholangiocarcinoma

Cholangiocarcinoma (CCA) most occurs from epithelium of hepatic biliary trees.54 From the past until now, the incidence of CCA increased constantly in population worldwide. Major patients are at the advanced stages and unable to undergo surgical because of seriously invasive and metastatic characteristics of CCA. Moreover, surgical intervention carries a significantly higher recurrence rate. Radical resection may be the only one effective treatment at present.55 Thus, novel biomarkers and effective therapeutic targets for the effectively detection and treatment of CCA are absolutely needed.

Xu et al56 found that the levels PANDAR were meaningfully enhanced both in tumour tissue and CCA cell lines. Higher levels of PANDAR were significantly relevant to lymph node invasion, TNM stage and recurrence. It would say that PANDAR might be an independent prognostic biomarker of CCA. To shed light on the effect of PANDAR, the authors downregulated PANDAR in CCA cell lines indicating that deceased of PANDAR could inhibit CCA cell proliferation. Moreover, the authors detected the expression of caspase‐3 and caspase‐9 after downregulation of PANDAR. Knockdown of PANDAR could increase the expression of caspase‐3 and caspase‐9. Furthermore, further experiment indicated that silenced PANDAR inhibited the levels of Bcl‐2 and enhanced the expression of Bax. Those results showed PANDAR inhibited cell apoptosis associated with caspase‐3, caspase‐9, Bcl‐2 and Bax. In addition, EMT is significantly correlated with cell migration and invasion. Xu et al56 revealed the knockdown of PANDAR detected that the decreased of N‐cadherin and Vimentin, but the levels of E‐cadherin were enhanced followed. Thus, potential mechanisms of PANDAR correlated with EMT pathway in vitro. Taken together, PANDAR may show as a novel therapeutic biomarker for CCA patients (Figure 4).

Figure 4.

Figure 4

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Knockdown of PANDAR‐boosted cell apoptosis via downregulated the levels of Bcl‐2, caspase‐3, caspase‐9 and upregulated Bax. Knockdown of PANDAR‐restrained cell invasion via downregulated the levels of N‐cadherin, Vimentin and upregulated E‐cadherin

2.6. Osteosarcoma

Osteosarcoma (OS) is the most famous primary malignant bone tumour, which occurring generally in adolescents and young adults.57 Previously results showed that over 20% of the young‐onset osteosarcoma patients presented with distant metastases at diagnosis, and more than 40% cases at advanced stages progress to metastasis during therapy.58 Patient life quality has been improved; thanks to the neoadjuvant chemotherapy. However, the toxicity, lung metastases and in situ recurrence still threaten many osteosarcoma patients.59 Therefore, it is necessary to discover and develop new prognostic targets in monitoring progression and survival of osteosarcoma in clinic.

Kotake et al60 found that PANDAR was highly expressed in the human OS cell line, compared with other cell lines. The authors further investigated the roles of PANDAR depletion on the cell cycle. As the result showed, downregulated of PANDAR resulted in increasing the proportion of cells in the G1 phase and decreasing the proportion of cells in the S and G2/M phases. Furthermore, qRT‐PCR assay results suggested that silence of PANDAR meaningfully increased the mRNA levels of P18. Previous experiment has demonstrated that P18, a member of the INK4 family, is thought as the characters of human tumour suppressors.61 It revealed that PANDAR was involved in the repression of P18 transcription. In conclusion, Kotake et al60 revealed that PANDAR promoted cell proliferation by repressing P18 expression and cell apoptosis, leading to oncogenic transformation.

2.7. Thyroid cancer

Thyroid cancer (TC), is one of the most usual malignant tumours of endocrine organs, originating from follicular or parafollicular thyroid cells.62 It was reported that TC was steadily increasing in morbidity and mortality over the years. According to epidemiological data, the incidence of TC has been increased by an average of 4.5% per year from 2007 to 2011 in the United States.63 Radiation, chemotherapy and surgery are the common treatment methods for thyroid cancer, unfortunately they all produce poor satisfaction. Therefore, it is urgent to explore precise diagnostic biomarkers and effective therapeutic targets.

Li et al64 found the expression of PANDAR was boosted both in TC and cell lines. Downregulation of PANDAR impaired proliferation and invasion in vitro. Moreover, knockdown of PANDAR showed a decrease in the percentage of cells at the S phase and a marked accumulation in the percentage of cells at the G0/G1 phase. Furthermore, cell cycle‐related protein expression including cyclin D1, Chk1 and Cdc25A was meaningfully decreased after suppressing of PANDAR. Importantly, the authors detected the expression of Bcl‐2 and Bax protein after knockdown of PANDAR. As the result showed, silenced PANDAR inhibited the levels of Bcl‐2 and boosted the levels of Bax. It has indicated that downregulation of PANDAR increased apoptosis of TC cell lines by decreasing Bcl‐2 expression and activating Bax. In conclusion, PANDAR may function as a significantly oncogenic biomarker in TC in the future (Figure 5).

Figure 5.

Figure 5

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Knockdown of PANDAR‐induced cell cycle arrest at the G0/G1 phase and decreased in the percentage of cells in the S phases. Knockdown of PANDAR‐boosted cell apoptosis via downregulated the levels of Bcl‐2 and upregulated Bax. Knockdown of PANDAR‐restrained cell proliferation via downregulated the levels of cell cycle‐related protein expression including cyclin D1, Chk1 and Cdc25A

2.8. Other cancers

The levels of PANDAR were also enhanced involve hepatocellular carcinoma, gastric cancer and bladder cancer. Peng et al65 found the expression of PANDAR was boosted in hepatocellular carcinoma (HCC) tissues and cell lines. Importantly, the levels of PANDAR were meaningfully associated with liver cirrhosis, HBsAg, AFP levels, tumour nodule, vascular invasion and TNM stage. The higher levels of PANDAR were correlated with poorer survival and shorter recurrence of HCC patients. Moreover, decreased PANDAR meaningfully inhibited cell proliferation, colony formation and cycle progression of HCC in vitro. It indicated that PANDAR was a significantly tumour biomarker and therapeutic target.

Ma et al66 disclosed that the levels of PANDAR were meaningfully enhanced in gastric cancer tissues compared with adjacent tissues. Moreover, higher levels of PANDAR were associated with depth of invasion, TNM stage and lymphatic metastasis. It can conclude that higher levels of PANDAR may possess the character of potential prognostic biomarker in gastric cancer.

Zhan et al67 found that PANDAR was meaningfully upregulated in bladder cancer tissue and cell lines compared with paired‐adjacent non‐tumourous tissues, which also positively correlated with higher histological grade and advanced TNM stage. Moreover, increased PANDAR expression promoted cell proliferation and suppressed cell apoptosis. Similar to previous results, knockdown of PANDAR can significantly inhibit cell proliferation and induced cell apoptosis. These results demonstrated PANDAR was a significant tumour biomarker and therapeutic target in bladder cancer.

3. CONCLUSION

It has been shown that lncRNAs act as important regulators in the process of tumour formation. With the development of lncRNAs mechanism in tumour, its role in the tumour development is worth of exploring and summarizing. Previous studies have demonstrated that PANDAR was a well‐characterized oncogenic lncRNA and widely overexpressed in many tumours. PANDAR is upregulated in many types of cancer, including colorectal cancer, lung cancer, renal cell carcinoma, cholangiocarcinoma, osteosarcoma, thyroid cancer and other cancers. Upregulation of PANDAR was significantly associated with advanced tumour weights, TNM stage and overall survival. Furthermore, repressed of PANDAR would restrain proliferation, migration and invasion. But overexpression of PANDAR boosted cell apoptosis. The mechanism by which PANDAR mediates its actions is complex and involved with multiple factors. PANDAR is induced by a p53‐dependent manner. It interacts with the transcription factor NF‐YA to limit the expression of pro‐apoptotic genes in many cancer cells. Nevertheless, the complex mechanisms of PANDAR involved in cancer development are still in the early stage. Therefore, multiple effects between PANDAR and target molecular markers should be explored in great depth. Further study on the clinic application of PANDAR and the related pathways is needed.

In conclusion, the current studies indicate that PANDAR may act as a powerful tumour biomarker for cancer diagnosis and treatment. Combined use of PANDAR and conventional tumour markers may be a promising direction of clinical diagnosis.

ACKNOWLEDGEMENTS

This work was funded by the National Key Basic Research Program of China (973 Program) (2014CB745201), the Chinese High‐Tech (863) Program (2014AA020607), National Natural Science Foundation of China [81402103], International S&T Cooperation program of China (ISTCP) (2014DFA31050), The National Science Foundation Projects of Guangdong Province (2014A030313717), the Shenzhen Municipal Government of China (ZDSYS201504301722174, JCYJ20150330102720130, GJHZ20150316154912494), and Special Support Funds of Shenzhen for Introduced High‐Level Medical Team.

CONFLICT OF INTEREST

The authors declare that they have no competing interests.

Zou Y, Zhong Y, Wu J, et al Long non‐coding PANDAR as a novel biomarker in human cancer: A systematic review. Cell Prolif. 2018;51:e12422 10.1111/cpr.12422

Contributor Information

Yuchen Liu, Email: liuyuchenmdcg@163.com.

Fuyou Zhang, Email: zhangfuyou666666@163.com.

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