Involvement of lncRNA in cancer diagnosis and prognosis and clinical implications

Abstract

Long non-coding ribonucleic acids (lncRNAs) form a subclass of non-coding RNAs (ncRNAs), they are quite long and as their name non-coding suggests they do not have a role in protein coding. lncRNAs are vital in all the key steps of tumorigenesis, such as epithelial-mesenchymal transition, cancer stem cells formation, invasion, migration, and formation of the tumor vasculature. lncRNAs are classified into oncogenic or anti-tumor lncRNAs based on their functions. Moreover, cancer stem cells show an extremely specific pattern of expression of lncRNAs, which can be used for early detection of cancer. Similarly, their pre-treatment expression levels correlate with prognosis as they participate in key tumor biology processes like metastasis and recurrence. This chapter seeks to explore both the association between lncRNA genes and cancer and the role of lncRNAs in cancer initiation and progression. Future questions would focus on what the accepted normal ranges of lncRNA expression will be, where they are present in body fluids, which could help with non-invasive tests. But for now, one thing is clear that lncRNAs could pave the way for novel cancer therapies.

Introduction

It is well known that the early diagnosis of cancer is essential for increasing survival rates and improving the quality of treatment. Cancer is responsible for around 19.9 million new cases and 9.7 million deaths worldwide, according to the World Health Organization [1]. Laying the groundwork for increased awareness among all stakeholders, early diagnosis of cancer includes work on numerous questions: Who is the most probable candidate for developing cancer? What is the biology and progression of precancerous and early-stage disease that warrants intervention? Their answers must be woven into sensitive and specific early detection technologies that should be supported by effective clinical evaluation. Interdisciplinary collaboration is important; the timing relative to technological and biological progress emphasizes the need to hasten early detection research ‘to change the game’ in terms of cancer survival. Research into multi-faceted novel molecules, such as long non-coding ribonucleic acids (lncRNAs), is likely to facilitate easy and non-invasively effective detection and targeted therapy [2]. Non-coding RNAs (ncRNAs) encompass a wide range of RNA classes that are always actively involved in operating, such as X-chromosome maintenance, epigenetic control, genomic imprinting, gene regulation during the post-transcriptional phase like mRNA splicing, etc. [3]. Furthermore, they fall into small (18–200 nt) and long (lncRNAs, > 200 nt) classes of regulatory ncRNAs [2]. Long non-coding RNAs can also originate from transcriptional pseudogenes or mitochondrial genes, antisense to the untranslated regions or promoter regions of protein-coding genes and can be bi-directional from intergenic regions. These are the RNA polymerase type II transcripts that have undergone capping at the 5’ end, addition of a series of adenosine residues at the 3’ end (polyadenylation), and splicing [4]. Non-coding RNAs can be found in the cytosol and nucleus of a cell and has the ability to alter gene expression at the epigenetic level, transcription stage, and in the post transcription stage as well. Within the class of non-coding RNAs, lncRNAs can be classified into at least four major archetypes: archetype I, archetype II, archetype III, and archetype IV. Archetype I lncRNAs operate as molecular switches; “dominant blackhole” proteins are archetype II lncRNAs that act as decoys binding and “hiding” the proteins, and ribonucleoprotein complex gene-targeting proteins are synthesized as archetype III lncRNAs [5]. The lncRNAs of archetype IV serve as a foundation for the complexation of several proteins [4].

What are lncRNAs and why do they matter?

Before diving into their potential, let us clarify what ncRNAs are, and how they differ from coding RNAs? Coding RNAs include messenger RNAs (mRNAs), which function as templates for protein synthesis [6]. These are the workhorses of cellular machinery, carrying genetic instructions to produce proteins that perform countless vital functions [7]. Non-coding RNAs (ncRNAs), on the other hand, are RNA molecules that do not encode proteins [8]. Despite their name, they are far from useless; they play diverse regulatory roles in gene expression and cellular processes. Among the vast family of ncRNAs, lncRNAs are defined by their length — over 200 nucleotides — and their functional versatility [3]. Unlike mRNAs, which directly produce proteins, lncRNAs function as sophisticated regulators, influencing cellular functions in multiple ways:

• chromatin remodelling: lncRNAs can modify the structure of chromatin, controlling gene accessibility and activity [9];

• transcriptional regulation: these factors interact with RNA polymerase and transcription factors to either enhance or suppress gene expression [10].

• post-transcriptional modulation: by affecting mRNA splicing, stability, or translation, lncRNAs fine-tune protein production [11].

The discovery of non-coding DNA sequences, once dismissed as “junk DNA”, has led to a deeper understanding of genomics and their critical roles in cellular communication and disease processes. Advanced sequencing technologies and bioinformatics tools have allowed scientists to analyze non-coding regions of the genome more thoroughly, identifying their involvement in gene regulation and expression [12]. This has led to groundbreaking insights into their significance, which has implications for personalized medicine. By understanding a person’s unique genomic makeup, doctors can tailor treatments to improve efficacy and reduce adverse effects. Additionally, genomic sequences could help identify genetic predispositions to certain diseases, enabling early intervention and preventive care.

lncRNAs and cancer — a revolutionary partnership

lncRNAs play a crucial role in cancer research, regulating gene expression, influencing tumor growth, metastasis, and modulating cellular processes like proliferation, apoptosis, and differentiation. They can also serve as biomarkers for diagnosis and targets for therapeutic intervention. lncRNAs can be classified as oncogenic or tumour-suppressor lncRNAs, depending on their dysregulation [13]. They collaborate with microRNAs (miRNAs) to regulate transcription and cellular pathways, acting as molecular sponges [14]. Their tissue-specific expression and stability in body fluids make them powerful candidates for cancer diagnostics. Encapsulated within exosomes, lncRNAs circulate in blood, urine, and saliva, offering an opportunity for non-invasive liquid biopsies. Early cancer detection significantly improves treatment outcomes and increases survival rates. By identifying cancer at an initial stage, interventions can be more effective, and patients have access to a wider range of treatment options.

Future perspectives: lncRNAs in diagnostics and prognosis

lncRNAs play a pivotal role in cancer management thanks to their integration into clinical practice. Compared to traditional biomarkers, such as proteins [carcinoembryonic antigen (CEA), alpha-fetoprotein] or mutation based biomarkers (EGFR, BRCA1, BRCA2, etc.), they have high specificity and stability [15, 16]. Through lncRNA profiling, early detection could be facilitated in the following ways:

• enable the identification of cancer in its earliest stages, improving survival rates;

• offer insights into tumour subtypes, guiding personalised therapies;

• monitor treatment responses and disease progression through non-invasive tests;

lncRNAs, such as HOX antisense intergenic RNA (HOTAIR) and MEG3, can signal aggressive tumor behavior and indicate therapeutic responsiveness, allowing for early intervention and targeted therapies [17]. Challenges like standardization and validation remain, but are being overcome by advancements in genomics and bioinformatics. The future of cancer diagnostics could resemble routine blood tests, with lncRNA profiles guiding clinical decisions. Early detection can lead to targeted therapies, potentially lowering healthcare costs. lncRNA metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) is associated with poor prognosis in several cancers, highlighting its potential as a prognostic biomarker [18]. Understanding the roles of lncRNAs like MALAT1 in cancer can enhance diagnostic precision and treatment outcomes. lncRNAs hold significant promise in personalized medicine, providing insights into an individual’s molecular landscape, leading to tailored therapeutic strategies targeting lncRNA-driven pathways. Integrating lncRNA profiling into clinical practice can optimize treatment regimens, improve patient outcomes, and reduce unnecessary interventions. lncRNAs can transform cancer diagnostics from invasive methods to precise, non-invasive, and highly personalized approaches [19]. The answer lies in continued research and clinical innovation, but the possibilities are boundless.

Role of lncRNAs in cancer diagnosis

lncRNAs have emerged as a promising new frontier in cancer diagnosis, offering earlier detection, more accurate classification, and personalized treatment strategies [20]. Their unique characteristics and diverse mechanisms make them ideal candidates for revolutionizing cancer identification and management. lncRNAs present different expression patterns in various cancer types, making their detection in tumor cells possible. Tissue-specific expression allows for the determination of cancer origin and differentiation between different cancer types [21]. Some lncRNAs are more specific to liver cells, while others are specific to lung tissue alone, determining the predominant site of cancer and appropriate treatment. lncRNAs are often dysregulated in cancer cells, overexpressed or underexpressed, which serves as an indicator for the presence of cancer. Various techniques, such as quantitative reverse transcription polymerase chain reaction (qRT-PCR), RNA sequencing (RNA-Seq), and in-situ hybridization, can be used to measure the levels of lncRNA and identify specific expression patterns associated with various cancers. qRT-PCR converts RNA to complementary DNA (cDNA) and amplifies it using PCR, while RNA-Seq provides a comprehensive view of the lncRNA transcriptome, allowing easy identification and quantification of known and novel lncRNAs. In situ hybridization visualizes lncRNA expression in tissues using labelled probes, allowing for detection at the individual cell level and spatial localization of expression patterns [22].

Potential biomarkers for early cancer detection

lncRNAs, or non-coding RNAs, have the greatest promise for early cancer detection and monitoring. They can be detected in bodily fluids like blood, urine, and saliva, making their testing process non-invasive. This is an improvement over the traditional biopsy method. lncRNAs are more sensitive and specific than traditional cancer biomarkers, allowing them to identify cancer at an early stage with higher specificity, leading to earlier intervention and better treatment. Detection of cancer at an early stage by lncRNA-based diagnostics can improve patient outcomes and potentially save lives. Liquid biopsies, a new method of cancer diagnosis, use material derived from a tumor to analyze it from bodily fluids. lncRNAs are prime candidates for liquid biopsies due to their stability in these fluids and their ability to be attacked by mechanisms such as exosomes for degradation [23]. Liquid biopsies have advantages over tissue biopsies, including being less invasive, easier to perform, and allowing for more frequent monitoring. Potential applications of lncRNA-based liquid biopsies include early cancer detection, monitoring treatment response, detecting recurrence or metastasis, and personalized medicine. In summary, lncRNAs are emerging as promising biomarkers for early cancer detection and monitoring, with their tissue specificity, alterations in expression levels in cancer cells, and presence in bodily fluids positioning them as promising biomarkers for early detection and disease monitoring. The development of lncRNA-based liquid biopsies could transform the approach to cancer care worldwide.

Role of lncRNAs in cancer prognosis

lncRNAs have significantly impacted gene expression, particularly in cancer. While not suitable for disease diagnosis, lncRNAs can be used for prognosis, offering patient outcomes that can be used to determine therapeutics and understand disease progression. lncRNAs are key modulators of tumor response to radiotherapy and immunotherapy. In radiotherapy, several lncRNAs influence radiosensitivity by regulating DNA repair mechanisms such as LINP1 (lncRNA in non-homologous end joining pathway 1) enhances DNA double-strand break repair via the non-homologous end joining (NHEJ) pathway, contributing to radio-resistance in cervical cancers [24]. Similarly, HOTAIR has been shown to promote resistance towards radiotherapy through modulation of DNA repair genes and chromatin remodelling, while growth arrest-specific 5 (GAS5), a tumor-suppressive lncRNA, enhances radiosensitivity by inhibiting DNA repair and promoting apoptosis [25]. lncRNAs also play a pivotal role in shaping the tumor immune microenvironment such as NEAT1 and LINK-A have been implicated in modulating the expression of immune checkpoint molecules like programmed death-ligand 1 (PD-L1), thereby influencing tumor immune evasion and responsiveness to immune checkpoint inhibitors [26]. Additionally, lnc-EGFR has been shown to promote regulatory T cell (Treg) differentiation and suppress cytotoxic T lymphocyte activity in hepatocellular carcinoma, contributing to immune suppression and poor immunotherapeutic outcomes [27].

This article focuses on the multicentric functions of lncRNAs in cancer prognosis, potentially leading to personalized oncology. Some lncRNAs are directly connected to cancer progression and clinical outcome, predicting aggressiveness, recurrence, and survival chances. A correlation was found between several lncRNAs and clinical parameters like stage, grade, and metastasis through lymph node involvement, allowing for prediction of patient outcomes. HOTAIR, a highly studied lncRNA, has been associated with various cancers, with overexpression associated with greater malignancy, increased metastasis, and poorer survival rates [28]. MALAT1, a metastasis-associated lung adenocarcinoma transcript 1, was associated with poor prognosis and metastasis in lung cancer [29]. GAS5 is a tumor suppressor like oncogenic lncRNAs, with low expression associated with poor prognosis outcomes in cancerous diseases like breast and prostate cancer [30]. The study of lncRNAs, or non-coding RNAs, has revolutionized the prognosis of cancer patients. By measuring the expression levels of these RNAs, clinicians can categorize patients into risk groups, enabling proper strategic treatment. Prognostic lncRNA signatures, which integrate expression data from multiple lncRNAs, provide more accurate and reliable outcome predictions. Examples of lncRNA signatures include HOTAIR, MALAT1, and prostate cancer-associated transcript 1 (PCAT-1), which are considered a panel for the prognosis of prostate cancer [31]. lncRNA signatures offer deeper insights into tumor biology, enhance the prediction of disease recurrence and metastasis, and help identify higher-risk patients who may be closely followed or subjected to therapies. The revolution in cancer prognosis may come from the ongoing efforts in discovering and validating lncRNA-based signatures. Predictive biomarkers, such as urothelial carcinoma associated 1 (UCA1), colon cancer-associated transcript 2 (CCAT2), and nuclear paraspeckle assembly transcript 1 (NEAT1), can be used to predict treatment responses and increase efficacy [32]. These biomarkers can be used in targeted therapies and limit side effects aiding medical benefit. lncRNA profiling in clinics allows for the selection of therapies that are likely to work for the patient’s molecular profile. The dynamic expression of lncRNAs over time indicates therapy effect and can be monitored in real time. Changes in lncRNA expressions because of treatment can be used as markers of emerging resistance. Monitoring would provide the time-changing nature of treatment strategies towards better patient outcomes. lncRNAs can also be used in monitoring disease progression, providing a long-term warning of recurrence or metastasis. Recurrence alerts are crucial in oncology, as they can be detected when the tumor is enlarged. Blood-borne circulating levels of lncRNAs can dramatically change before clinical or imaging evidence of recurrence, leading to timely intervention and minimizing the risk of recurrent disease [33]. Metastasis through spread is one of the most significant causes of mortality, and lncRNAs play a significant role in processes related to epithelial-mesenchymal transition (EMT), migration, and invasion. Epithelial-mesenchymal transition (EMT)-related lncRNAs, such as HOTAIR and zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1), can be used to predict metastasis and help decide on systemic therapies and surveillance strategies [34]. The future perspective for lncRNAs in cancer prognosis is promising, as they will be integrated into clinics with genomic, proteomic, and imaging data. Artificial Intelligence and machine learning algorithms will decode complex lncRNA expression patterns, identifying new biomarkers and signatures [35]. Combining lncRNA with liquid biopsies could enhance sensitivity and specificity in cancer assessment. lncRNAs represent an excellent class of prognostic tools in oncology, allowing for prediction of clinical results, treatment strategies, and disease progression. With their prognostic capability, physicians may be able to personalize cancer therapies. Future research will reveal further functions of lncRNAs and improve their clinical applications, thereby enhancing patient outcomes and quality of life.

Clinical applications of lncRNAs in cancer management

It has been established that long non-coding RNAs play a vital role in inhibiting and promoting processes in normal and cancerous cells, and the new era of exciting opportunities to tackle cancer stands widely open (Fig. 1). Several lncRNAs have been identified as potential oncogenic drivers or tumor suppressors in various cancer types. Table 1 highlights some notable lncRNAs and their roles. The current scope goes far beyond simply making predictions as to the outcome of the disease, as lncRNAs have become a means to guide the development of targeted therapies. This article investigates the clinical use of lncRNAs and their ability to assist in providing personalized medicine, targeted therapy and the difficulty of integrating new lncRNA technologies into the clinic.

Figure 1.

Different long non-coding ribonucleic acid (lncRNA) involvement in specific cancers. EMT — epithelial-mesenchymal transition. HOTAIR — HOX antisense intergenic RNA; MALAT1 — metastasis-associated lung adenocarcinoma transcript-1; CCAT2 — colon cancer-associated transcript 2; P-CAT1 — prostate cancer associated transcript 1; HULC — highly up-regulated in liver cancer; TUG1 — taurine upregulated gene 1

Table 1.

Long non-coding ribonucleic acids (lncRNAs) and their roles

S. NO.	lncRNA	Role in cancer	Expression	References
1.	BCAL8	Regulates tumor growth and metastasis, implicated in breast cancer	Upregulated	[36]
2.	SAMMSON	Overexpressed in melanoma, promotes cancer cell survival and mitochondrial function	Upregulated	[37]
3.	CCAT2	Drives metastasis and Wnt signaling pathway in breast cancer	Upregulated	[38]
4.	LINC00673	Regulates cancer cell proliferation in breast cancer	Upregulated	[39]
5.	CONCR	Key role in DNA replication and cancer cell proliferation in colorectal cancer	Upregulated	[40]
6.	LINP1	Involved in DNA damage repair and radioresistance in breast cancer	Upregulated	[41]
7.	SLNCR1	Recruits the androgen receptor to EGR1-bound genes in melanoma and inhibits expression of tumor suppressor p21	Upregulated	[42]
8.	NKILA	Functions as a tumor suppressor by inhibiting NF-κB signaling, reducing metastasis in breast cancer	Downregulated	[43]
9.	MAYA	Regulate cancer signaling pathways in colorectal cancer	Upregulated	[40]
10.	GClnc1	Drives ovarian cancer progression by regulating p53 signaling pathway	Upregulated	[44]
11.	LINK-A	Promotes TNBC progression via HIF1α signaling	Upregulated	[45]
12.	NRCP	Promotes proliferation, metastasis and glycolysis in ovarian cancer	Upregulated	[46]
13.	SNHG5	Upregulated in colorectal cancer, promotes survival	Upregulated	[47]
14.	SNHG1	Associated with tumor proliferation, especially in colorectal and lung cancer	Upregulated	[48]
15.	Lnc-EGFR	Regulates EMT and EGFR signaling in relapsing-remitting multiple sclerosis	Upregulated	[49]
16.	NEAT1	Overexpressed in bladder cancer, promoting cell proliferation and resistance to apoptosis	Upregulated	[50]
17.	lncARSR	Mediates drug resistance in non-small cell lung cancer by regulating PTEN/protein kinase B (Akt) pathway	Upregulated	[51]
18.	HOXD-AS1	Promotes cancer growth and metastasis, particularly in hepatocellular carcinoma	Upregulated	[52]
19.	N-BLR	Involved in gastric cancer metastasis	Upregulated	[52]
20.	H19	Oncogenic lncRNA, promoting tumor growth and drug resistance in gastric cancer	Upregulated	[53]
21.	PTAR	Regulates EMT and metastasis in serous ovarian cancer	Upregulated	[54]
22.	MEG8	Acts as an oncogene in lung and pancreatic cancer	Upregulated	[55]
23.	MALAT1	Enhances cancer cell migration, invasion, and metastasis in lung cancer	Upregulated	[52]
24.	ATB	Promotes EMT and metastasis in hepatocellular carcinoma	Upregulated	[56]
25.	CRYBG3	Inhibits proliferation, migration and invasion of lung cancer cells through direct interaction with G-actin preventing its polymerization to F-actin	Downregulated	[52]
26.	LINC00857	Regulates cancer metabolism and progression in pancreatic cancer	Upregulated	[52]
27.	LCAT1	Functions as an oncogene in lung cancer	Upregulated	[52]
28.	DANCR	Associated with drug resistance and metastasis in hepatocellular carcinoma	Upregulated	[52]
29.	LINC00452	Promotes tumor progression in ovarian cancer	Upregulated	[52]
30.	ZNFX1-AS1	Acts as an oncogene by regulating immune responses in hepatocellular carcinoma	Upregulated	[57]
31.	HOTAIR	Oncogene linked to metastasis and poor prognosis in NSCLC	Upregulated	[58]
32.	XIST	Promotes proliferation and inhibits apoptosis in thyroid cancer	Upregulated	[59]
33.	Gm26809	Induced melanoma cells proliferation and migration through reprogramming of normal fibroblasts into CAFs	Upregulated	[52]
34.	LINC00092	Supports glycolysis in ovarian cancer, aiding metastasis	Upregulated	[60]
35.	NR2F1-AS1	Regulates EMT and cancer stemness in breast cancer	Upregulated	[61]
36.	FILNC1	Regulates metabolism and stress responses in renal cancer	Upregulated	[62]
37.	AC104041	Acts as ceRNA for miR-6817-3p, inducing Wnt2B ligand stabilization and β-catenin activation allowing head and neck squamous cell carcinoma cells proliferation and metastasis	Upregulated	[63]
38.	LINC00680	Promotes tumor progression in esophageal squamous cell carcinoma	Upregulated	[64]
39.	LINC00312	Acts as a tumor suppressor in NSCLC	Upregulated	[65]
40.	Linc-UBC1	Overexpressed in bladder cancer, enhancing tumor growth	Upregulated	[66]
41.	TROJAN	Promotes proliferation and invasion in breast cancer	Upregulated	[67]
42.	MDC1-AS	Regulates cancer proliferation and apoptosis in glioma	Upregulated	[68]
43.	MEG3	Tumor suppressor that inhibits cancer cell growth in tongue squamous cell carcinoma	Downregulated	[69]
44.	MIR31HG	Regulates cell cycle and EMT in colorectal cancer	Upregulated	[70]
45.	NBR2	Acts as a tumor suppressor by regulating AMPK signaling in thyroid cancer	Downregulated	[71]
46.	ncRAN	Promotes tumorigenesis in colorectal and other cancers	Upregulated	[72]
47.	TMPO-AS1	An oncogene, promotes tumor by acting as a ceRNA for various miRNAs in NSCLC	Upregulated	[73]
48.	PCAT-1	Involved in prostate cancer progression	Upregulated	[74]
49.	PVT1	Oncogene regulating cell proliferation and apoptosis resistance in nasopharyngeal carcinoma	Upregulated	[75]
50.	SChLAP1	Leads to aggressive prostate cancer	Upregulated	[76]
51.	SPRY4-ITI	Promotes EMT and invasion in lung cancers	Upregulated	[77]
52.	TUG1	Regulates proliferation, apoptosis, and drug resistance in acute myeloid leukemia	Upregulated	[78]
53.	UCA1	Enhances drug resistance and cancer metastasis in gastric cancer	Upregulated	[79]
54.	BCAR4	Promotes breast cancer progression and metastasis	Upregulated	[80]
55.	ARSR	Involved in drug resistance and metastasis in colorectal cancer	Upregulated	[81]
56.	ANRIL	Associated with laryngeal squamous cell carcinoma, promoting proliferation and invasion	Upregulated	[82]
57.	CASC2	Functions as a tumor suppressor, inhibiting melanoma cancer cell growth	Upregulated	[83]
58.	ERINA	Promotes cell proliferation and progression of cell cycle in breast cancer	Upregulated	[84]
59.	LET	Inhibits metastasis and acts as a tumor suppressor	Downregulated	[85]

EGR1 — epidermal growth factor receptor 1; NF-κB — nuclear factor kappa B; HIF1α — hypoxia-inducible factor 1 alpha; TNBC — triple-negative breast cancer; miRNAs — micro RNA; EMT — epithelial-mesenchymal transition; PTEN — phosphatase and tensin homologue; NSCLC — non-small cell lung cancer; CAFs — cancer-associated fibroblasts; ceRNA — competing endogenous ribonucleic acid; AMPK — AMP-activated protein kinase

Personalized treatment according to lncRNA-expression

Personalized medicine aims to tailor cancer treatment to an individual patient’s molecular profile, with lncRNAs being a valuable tool in this regard. lncRNA expression profiling helps clinicians identify subgroup patients with unique molecular and clinical characteristics, allowing for the stratification of patients and the development of targeted treatment strategies. For instance, the lncRNA HOTAIR is upregulated in aggressive cancers, such as breast and colorectal cancers. lncRNAs can also function as predictive biomarkers to predict how a patient might react to specific therapies. For example, prominent levels of the lncRNA UCA1 are associated with chemoresistance in bladder cancer [86], while the lncRNA MALAT1 predicts resistance to tyrosine kinase inhibitors in non-small cell lung cancer [87]. By incorporating lncRNA gene expression data into clinical decision-making, doctors and clinicians can avoid administering ineffectual treatments and optimize treatment selection. Real-time monitoring of lncRNA during treatment offers significant feedback on therapy effectiveness, providing the basis for immediate clinician adjustment of strategies. For example, suppressing tumor-promoting lncRNAs during chemotherapy may be considered an indicator of tumor, while continuing expression suggests resistance or recurrence.

lncRNAs are not only biomarkers but also actionable targets for therapy due to their cancer-specific expression and regulatory functions. Antisense ligonucleotides (ASOs) are artificial synthetic DNA or RNA strands that strongly interact only with specific target lncRNAs [88]. CRISPR-Cas9 gene editing technology can disrupt lncRNA genes with precise editing capability, particularly promising for oncogenic lncRNAs that are behind cancer progression [89]. Small molecules can be designed to target lncRNAs themselves or disrupt interactions between lncRNAs and proteins or DNA. RNA interference (RNAi) technologies, including siRNAs and shRNAs, can selectively silence lncRNAs, inhibiting cell proliferation [90]. lncRNAs exist with distinct secondary and tertiary structures that may offer an additional route for targeting therapeutic intervention. Small molecules or aptamers that could disrupt these structures might interfere with their functions. For example, the compound TMPyP4 disrupts the G-quadruplex structures in the lncRNA NEAT1 and can inhibit its protein interaction with the nucleus, suppressing cancer cell survival [91]. However, the translation of lncRNA into clinical practice remains an enormous challenge. Challenges include delivery and specificity, off-target effects, the complexity of lncRNA biology, standardization and validation, and cost and access. Advances in delivery systems and viral vectors are being investigated for improved specificity and efficiency. Standardized protocols for lncRNA-based diagnostics and therapeutics are needed to standardize different clinical settings for high reproducibility and comparability. Cost and access are also crucial, as the production and development of lncRNA-based therapies are expensive and may not be easily accessible in resource-poor settings. In conclusion, lncRNAs are revolutionizing the fight against cancer through personalized treatment options, new targets for therapy, and accuracy in diagnostics. However, challenges such as delivery, specificity, and cost remain significant obstacles to overcome. As the biology of lncRNA continues to unfold in important research, it is poised to become a central molecule of precision oncology, ensuring survival and quality of life for cancer patients worldwide.

Conclusion

This chapter explores the role of lncRNAs, a class of RNA molecules that regulate gene expression and cellular processes. lncRNAs play a crucial role in cancer biology, playing a key role in all stages of carcinogenesis, from initiation and growth to metastasis and drug resistance. They hold great potential for clinical applications in cancer management, serving as biomarkers for diagnosis and prognosis, enabling early detection, accurate classification, and personalized treatment strategies. Early diagnosis can detect cancer at its earliest stages, increasing the chances of successful treatment and survival. Personalized treatment can be predicted based on patient subgroups with different prognoses, leading to more effective and tailored treatment strategies. Targeted therapies can also be targeted directly for therapeutic intervention, offering new avenues for cancer treatment and overcoming drug resistance. Future cancer research and treatment strategies are expected to see the development of new biomarkers, novel therapeutic approaches, precision medicine, and integration with other technologies. As our understanding of lncRNA biology deepens, we can expect to see more innovative and impactful applications of these molecules in the fight against cancer. In conclusion, lncRNAs represent a promising new frontier in cancer research and treatment, with their diverse functions and clinical applications having the potential to revolutionize cancer care and improve patient outcomes. Despite their promise, there are several challenges in integrating lncRNAs into current cancer therapies. One major hurdle is the complexity of lncRNA functions and their context-dependent roles, which require comprehensive understanding before clinical application. Additionally, developing effective delivery systems and ensuring the stability of lncRNAs in vivo pose significant technical challenges that must be overcome to harness their full therapeutic potential. To successfully address these challenges, interdisciplinary collaboration is essential. By bringing together experts in molecular biology, bioinformatics, clinical oncology, and pharmaceutical sciences, researchers can pool their knowledge and resources to unravel the complexities of lncRNA functions. Such collaboration can accelerate the development of innovative delivery systems and enhance the stability of lncRNAs in therapeutic applications, driving forward the integration of lncRNAs into cancer therapies.

Data availability statement

NA.