Exosomal Non-coding RNA Derived from Mesenchymal Stem Cells (MSCs) in Autoimmune Diseases Progression and Therapy; an Updated Review.

Inflammation and autoimmune diseases (AD) are common outcomes of an overactive immune system. Inflammation occurs due to the immune system reacting to damaging stimuli. Exosomes are being recognized as an advanced therapeutic approach for addressing an overactive immune system, positioning them as a promising option for treating AD. Mesenchymal stem cells (MSCs) release exosomes that have strong immunomodulatory effects, influenced by their cell of origin. MSCs-exosomes, being a cell-free therapy, exhibit less toxicity and provoke a diminished immune response compared to cell-based therapies. Exosomal non-coding RNAs (ncRNA), particularly microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are intricately linked to various biological and functional aspects of human health. Exosomal ncRNAs can lead to tissue malfunction, aging, and illnesses when they experience tissue-specific alterations as a result of various internal or external problems. In this study, we will examine current trends in exosomal ncRNA researches regarding AD. Then, therapeutic uses of MSCs-exosomal ncRNA will be outlined, with a particle focus on the underlying molecular mechanisms.

Connecting the dots: LncRNAs in the KRAS pathway and cancer.

Long non-coding RNAs (lncRNAs) have been identified as important participants in several biological functions, particularly their complex interactions with the KRAS pathway, which provide insights into the significant roles lncRNAs play in cancer development. The KRAS pathway, a central signaling cascade crucial for cell proliferation, survival, and differentiation, stands out as a key therapeutic target due to its aberrant activation in many human cancers. Recent investigations have unveiled a myriad of lncRNAs, such as H19, ANRIL, and MEG3, intricately modulating the KRAS pathway, influencing both its activation and repression through various mechanisms, including epigenetic modifications, transcriptional regulation, and post-transcriptional control. These lncRNAs function as fine-tuners, delicately orchestrating the balance required for normal cellular function. Their dysregulation has been linked to the development and progression of multiple malignancies, including lung, pancreatic, and colorectal carcinomas, which frequently harbor KRAS mutations. This scrutiny delves into the functional diversity of specific lncRNAs within the KRAS pathway, elucidating their molecular mechanisms and downstream effects on cancer phenotypes. Additionally, it underscores the diagnostic and prognostic potential of these lncRNAs as indicators for cancer detection and assessment. The complex regulatory network that lncRNAs construct within the context of the KRAS pathway offers important insights for the creation of focused therapeutic approaches, opening new possibilities for precision medicine in oncology. However, challenges such as the dual roles of lncRNAs in different cancer types and the difficulty in therapeutically targeting these molecules highlight the ongoing debates and need for further research. As ongoing studies unveil the complexities of lncRNA-mediated KRAS pathway modulation, the potential for innovative cancer interventions becomes increasingly promising.

Construction of a prognostic model for ovarian cancer based on a comprehensive bioinformatics analysis of cuproptosis-associated long non-coding RNA signatures.

Ovarian cancer (OCa) is a common malignancy in women, and the role of cuproptosis and its related genes in OCa is unclear. Using the GSE14407 dataset, we analyzed the expression and correlation of cuproptosis-related genes (CRGs) between tumor and normal groups. From the TCGA-OV dataset, we identified 20 cuproptosis-related long non-coding RNAs (CuLncs) associated with patient survival through univariate Cox analysis. OCa patients were divided into early-stage and late-stage groups to analyze CuLncs expression. Cluster analysis classified patients into two clusters, with Cluster1 having a poorer prognosis. Significant differences in "Lymphatic Invasion" and "Cancer status" were observed between clusters. Seven CRGs showed significant expression differences, validated using the human protein atlas (HPA) databases. Immune analysis revealed a higher ImmuneScore in Cluster1. GSEA identified associated signaling pathways. LASSO regression included 11 CuLncs to construct and validate a survival prediction model, classifying patients into high-risk and low-risk groups. Correlations between riskScore, Cluster phenotype, ImmuneScore, and immune cell infiltration were explored. Cell experiments showed that knocking down AC023644.1 decreases OCa cell viability. In conclusion, we constructed an accurate prognostic model for OCa based on 11 CuLncs, providing a basis for prognosis assessment and potential immunotherapy targets.

The potential role of circular RNAs in regulating p53 in different types of cancers.

P53 tumor suppressor is a major regulator of various cellular processes and functions. It has been reported that mutation or inactivation of p53 plays a crucial role in tumorigenesis in different types of cancers. Circular RNAs (circRNAs) are single-stranded non-coding RNAs that have significant post-transcriptional effects on the regulation of gene expression in various ways. These molecules can alter the expression and function of multiple genes and proteins. In the present study, we aimed to review circRNAs that regulate the expression, function, and stability of p53 and the possible interactions between these molecules and p53. Considering the importance of p53 in cancer and the network between p53 and circRNAs, future clinical trials targeting these circRNAs as therapeutic agents deserve worthy of attention.

Role of long non-coding RNAs (lncRNAs) in gastric cancer metastasis: A comprehensive review.

One of the greatest frequent types of malignancy is gastric cancer (GC). Metastasis, an essential feature of stomach cancer, results in a high rate of mortality and a poor prognosis. However, metastasis biological procedures are not well recognized. Long non-coding RNAs (lncRNAs) have a role in numerous gene regulation pathways via epigenetic modification as well as transcriptional and post-transcriptional control. LncRNAs have a role in a variety of disorders, such as cardiovascular disease, Alzheimer's, and cancer. LncRNAs are substantially related to GC incidence, progression, metastasis and drug resistance. Several research released information on the molecular processes of lncRNAs in GC pathogenesis. By interacting with a gene's promoter or enhancer region to influence gene expression, lncRNAs can operate as an oncogene or a tumor suppressor. This review includes the lncRNAs associated with metastasis of GC, which may give insights into the processes as well as potential clues for GC predicting and tracking.

Progress and trends in myocardial infarction-related long non-coding RNAs: a bibliometric analysis.

Background: Myocardial infarction (MI), a critical condition, substantially affects patient outcomes and mortality rates. Long non-coding RNAs (lncRNAs) play a critical role in the onset and progression of MI. This study aimed to explore the related research on MI-related lncRNAs from a bibliometric perspective, providing new clues and directions for researchers in the field. Methods: A comprehensive search was conducted on 7 August 2023, using the Web of Science Core Collection (WoSCC) database to compile a dataset of all English-language scientific journals. The search gathered all relevant publications from January 2000 to August 2023 that pertain to MI-related lncRNAs. Data on countries, institutions, journals, authors, and keywords were collected, sorted, statistically analyzed, and visualized using CiteSpace 6.2.R4, VOSviewer 1.6.19, an online bibliometric analysis platform (http://bibliometric.com), and the bibliometric package in R-Studio 4.3.1. Articles were screened by two independent reviewers. Results: Between January 2000 and August 2023, a total of 1,452 papers were published in the research field of MI-related lncRNAs. The year with the most publications was 2020, accounting for 256 papers. The publication volume displayed an exponential growth trend, fitting the equation y = 2.0215e0.2786x, R^2 = 0.97. In this domain, China leads in both the number of published papers (N = 1,034) and total citations, followed by the United States, Germany, Iran, and Italy. The most productive institution is Harbin Medical University (N = 144). The European Review for Medical and Pharmacological Sciences had the highest number of publications (N = 46), while Circulation Research had the most citations (TC = 4,537), indicating its irreplaceable standing in this field. Research mainly focuses on the cardiovascular system, cellular biology, physiology, etc. The most productive author is Zhang Y. Apart from "Myocardial Infarction" and "LncRNA," the most frequent keywords include "expression," "atherosclerosis," and "apoptosis." Cluster analysis suggests current research themes concentrate on cardiovascular diseases and gene expression, cardiac ischemia/reperfusion injury and protection, expression and proliferation, atherosclerosis and inflammatory response, among others. Keyword bursts indicate recent hot topics as targeting, autophagy, etc. Conclusion: This bibliometric analysis reveals that research on MI-related lncRNAs has rapidly expanded between January 2000 and August 2023, primarily led by China and the United States. Our study highlights the significant biological roles of lncRNAs in the pathogenesis and progression of MI, including their involvement in gene expression regulation, atherosclerosis development, and apoptosis. These findings underscore the potential of lncRNAs as therapeutic targets and biomarkers for MI. Additionally, our study provides insights into the features and quality of related publications, as well as the future directions in this research field. There is a long road ahead, highlighting the urgent need for enhanced global academic exchange.

Deciphering the Role of Necroptosis-Related Long Non-coding RNAs in Hepatocellular Carcinoma: A Necroptosis-Related lncRNA-Based Signature to Predict the Prognosis of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer, characterized by a high morbidity rate. Long non-coding RNAs (lncRNAs) play an important role in regulating various cellular processes and diseases, including cancer. However, their specific roles and mechanisms in HCC are not fully understood. This study used a multi-cohort design to investigate necroptosis-related lncRNAs (NRLs) in patients with HCC. We curated a list of 1095 NRLs and 838 genes showing differential expression between tumor and normal tissues. Among them, we found 105 NRLs closely associated with the prognosis of HCC patients. The 10 lncRNAs (AC100803.3, AC027237.2, AL158166.1, LINC02870, AC026412.3, LINC02159, AC027097.1, AC139887.4, AC007405.1, AL023583.1) generated by LASSO-Cox regression analysis were used to create a prognostic risk model for HCC and group patients into groups based on risk. The KEGG analysis revealed distinct pathway enrichments in high-risk (H-R) and low-risk (L-R) subgroups. According to GO analysis, this study identified 230 differentially expressed genes (DEGs) that were significantly enriched in specific biological processes. Comparison of immune checkpoint-related genes (MCPGs) between H-R and L-R patients revealed significant differences. Moreover, we established a correlation between the risk scores of patients with liver cancer and their sensitivity to 16 chemotherapeutic agents. Employing protein-protein interaction (PPI) analysis, we identified 10 hub genes that potentially regulate the molecular networks involved in HCC development. This study is a pioneering effort to investigate the roles of NRLs in HCC. It opens a new avenue for potential targeted therapies and provides insights into the molecular mechanisms of HCC.

Decoding LncRNA in COPD: Unveiling Prognostic and Diagnostic Power and Their Driving Role in Lung Cancer Progression.

Chronic obstructive pulmonary disease (COPD) and lung cancer represent formidable challenges in global health, characterized by intricate pathophysiological mechanisms and multifaceted disease progression. This comprehensive review integrates insights from diverse perspectives to elucidate the intricate roles of long non-coding RNAs (lncRNAs) in the pathogenesis of COPD and lung cancer, focusing on their diagnostic, prognostic, and therapeutic implications. In the context of COPD, dysregulated lncRNAs, such as NEAT1, TUG1, MALAT1, HOTAIR, and GAS5, emerge as pivotal regulators of genes involved in the disease pathogenesis and progression. Their identification, profiling, and correlation with the disease severity present promising avenues for prognostic and diagnostic applications, thereby shaping personalized disease interventions. These lncRNAs are also implicated in lung cancer, underscoring their multifaceted roles and therapeutic potential across both diseases. In the domain of lung cancer, lncRNAs play intricate modulatory roles in disease progression, offering avenues for innovative therapeutic approaches and prognostic indicators. LncRNA-mediated immune responses have been shown to drive lung cancer progression by modulating the tumor microenvironment, influencing immune cell infiltration, and altering cytokine production. Their dysregulation significantly contributes to tumor growth, metastasis, and chemo-resistance, thereby emphasizing their significance as therapeutic targets and prognostic markers. This review summarizes the transformative potential of lncRNA-based diagnostics and therapeutics for COPD and lung cancer, offering valuable insights into future research directions for clinical translation and therapeutic development.

Long non-coding RNAs in bone formation: Key regulators and therapeutic prospects.

Recent scientific investigations have revealed the intricate mechanisms underlying bone formation, emphasizing the essential role of long non-coding RNAs (lncRNAs) as critical regulators. This process, essential for skeletal strength and functionality, involves the transformation of mesenchymal stem cells into osteoblasts and subsequent deposition of bone matrix. lncRNAs, including HOX transcript antisense RNA (HOTAIR), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), differentiation antagonizing non-coding RNA (DANCR), and maternally expressed gene 3 (MEG3), have emerged as prominent players in this regulatory network. HOTAIR modulates osteoblast differentiation by interacting with chromatin-modifying enzymes, while MALAT1 regulates osteogenic differentiation through microRNA interactions. DANCR collaborates with Runx2 to fine-tune osteoblast differentiation, and MEG3 orchestrates multiple signaling pathways crucial for bone formation. Moreover, other lncRNAs such as H19, lncRNA for enhancing osteogenesis 3, rhabdomyosarcoma 2-associated transcript, urothelial cancer associated 1, taurine up-regulated gene 1, and nuclear enriched abundant transcript 1 contribute to the complex regulatory network governing osteoblast activities. Understanding the precise roles of these lncRNAs offers promising avenues for developing innovative therapeutic strategies targeting bone-related disorders like osteoporosis. Overall, this review summarizes the pivotal role of lncRNAs in bone formation, highlighting their potential as targets for future research endeavors aimed at advancing therapeutic interventions in bone diseases.

The Association between Long Non-Coding RNAs and Alzheimer's Disease.

Neurodegeneration occurs naturally as humans age, but the presence of additional pathogenic mechanisms yields harmful and consequential effects on the brain. Alzheimer's disease (AD), the most common form of dementia, is a composite of such factors. Despite extensive research to identify the exact causes of AD, therapeutic approaches for treating the disease continue to be ineffective, indicating important gaps in our understanding of disease mechanisms. Long non-coding RNAs (lncRNAs) are an endogenous class of regulatory RNA transcripts longer than 200 nucleotides, involved in various regulatory networks, whose dysregulation is evident in several neural and extraneural diseases. LncRNAs are ubiquitously expressed across all tissues with a wide range of functions, including controlling cell differentiation and development, responding to environmental stimuli, and other physiological processes. Several lncRNAs have been identified as potential contributors in worsening neurodegeneration due to altered regulation during abnormal pathological conditions. Within neurological disease, lncRNAs are prime candidates for use as biomarkers and pharmacological targets. Gender-associated lncRNA expression is altered in a gender-dependent manner for AD, suggesting more research needs to be focused on this relationship. Overall, research on lncRNAs and their connection to neurodegenerative disease is growing exponentially, as commercial enterprises are already designing and employing RNA therapeutics. In this review we offer a comprehensive overview of the current state of knowledge on the role of lncRNAs in AD and discuss the potential implications of lncRNA as potential therapeutic targets and diagnostic biomarkers in patients with Alzheimer's disease.

Long Non-Coding RNAs and Their Potential Role as Biomarkers in Inflammatory Bowel Disease.

Inflammatory bowel disease is a chronic inflammatory disease that encompasses entities such as Crohn's disease and ulcerative colitis. Its incidence has risen in newly industrialised countries over time, turning it into a global disease. Lately, studies on inflammatory bowel disease have focused on finding non-invasive and specific biomarkers. Long non-coding RNAs may play a role in the pathophysiology of inflammatory bowel disease and therefore they may be considered as potential biomarkers for this disease. In the present article, we review information in the literature on the relationship between long non-coding RNAs and inflammatory bowel disease. We especially focus on understanding the potential function of these RNAs as non-invasive biomarkers, providing information that may be helpful for future studies in the field.

Discovery of high-expressing lncRNA-derived sORFs as potential tumor-associated antigens in hepatocellular carcinoma.

BACKGROUND: This study is based on deep mining of Ribo-seq data for the identification of lncRNAs that have highly expressed sORFs in HCC. In this paper, dynamic prospects associated with sORFs acting as newly defined tumor-specific epitopes are discussed with possible improvement in strategies for tumor immunotherapy. OBJECTIVE: Using ribosome profiling to identify and characterize sORFs within lncRNAs in HCC, identify potential therapeutic targets and tumor-specific epitopes applicable for immunotherapy. METHODS: MetamORF performed the identification of sORFs with deep analysis of the data of ribosome profiling in lncRNAs associated with HCC. The translation efficiency in these molecules was estimated, and epitope prediction was done by pVACbind. Peptide search was done to check the presence of micropeptides translated from these identified sORFs. validated translational activity and identified potential epitopes. RESULTS: Higher translation efficiency was noted in the case of lncRNAs associated with HCC compared to normal tissues. Of particular note is ORF3418981, which results in the highest expression and has supporting experimental evidence at the protein level. Epitope prediction identified a putative epitope at the C-terminus of ORF3418981. CONCLUSIONS: This study uncovers the as-yet-unknown potential of lncRNA-derived sORFs as sources of tumor antigens, shifting the research focus from protein-coding genes to non-coding RNAs also in the HCC context. Moreover, this study highlights the contribution of a subset of lncRNAs, especially LINC00152, to the development of tumors and modulation of the immune response by its sORFs.

Diagnostic lncRNA high expression for liver patients prognosis and medication guidance: a systematic review and meta-analysis.

Background: The study of long non-coding RNAs (lncRNAs) has gained significant attention due to their roles in regulating gene expression and their potential as diagnostic biomarkers. This systematic review and meta-analysis aimed to evaluate the diagnostic value of high-expression lncRNAs in liver disease patients, including those with hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Methods: A comprehensive literature search was conducted across multiple electronic databases, including PubMed, Embase, Web of Science, and Cochrane Library, up to July 2024. Studies were included if they investigated the expression of lncRNAs in liver disease patients and evaluated their diagnostic performance. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to assess the quality of included studies. Pooled sensitivity, specificity, diagnostic odds ratios (DOR), and summary receiver operating characteristic (SROC) curves were calculated using a bivariate random-effects model. Results: Nine studies involving 888 samples were included in the meta-analysis. The pooled hazard ratio (HR) for overall survival (OS) was 2.01 (95% CI: 1.71-2.36), indicating a significant association between high lncRNA expression and poor liver disease outcomes. Subgroup analyses revealed a pooled odds ratio (OR) of 1.99 (95% CI: 1.53-2.60) for tissue samples and 8.62 (95% CI: 1.16-63.71) for blood samples, suggesting a stronger diagnostic value for blood-based lncRNAs. The funnel plots indicated minimal publication bias, and sensitivity analyses confirmed the robustness of the findings. Conclusion: High-expression lncRNAs show significant potential as diagnostic biomarkers for liver diseases, offering non-invasive, accurate, and timely diagnostic information. Despite the promising results, further research is needed to standardize detection methods, elucidate the biological functions of lncRNAs, and validate their clinical utility in diverse patient populations. Integrating lncRNA biomarkers with traditional diagnostic approaches could enhance diagnostic accuracy and improve patient management and outcomes in liver disease.

Genomic and Epigenomic Biomarkers of Immune Checkpoint Immunotherapy Response in Melanoma: Current and Future Perspectives.

Immune checkpoint inhibitors (ICIs) demonstrate durable responses, long-term survival benefits, and improved outcomes in cancer patients compared to chemotherapy. However, the majority of cancer patients do not respond to ICIs, and a high proportion of those patients who do respond to ICI therapy develop innate or acquired resistance to ICIs, limiting their clinical utility. The most studied predictive tissue biomarkers for ICI response are PD-L1 immunohistochemical expression, DNA mismatch repair deficiency, and tumour mutation burden, although these are weak predictors of ICI response. The identification of better predictive biomarkers remains an important goal to improve the identification of patients who would benefit from ICIs. Here, we review established and emerging biomarkers of ICI response, focusing on epigenomic and genomic alterations in cancer patients, which have the potential to help guide single-agent ICI immunotherapy or ICI immunotherapy in combination with other ICI immunotherapies or agents. We briefly review the current status of ICI response biomarkers, including investigational biomarkers, and we present insights into several emerging and promising epigenomic biomarker candidates, including current knowledge gaps in the context of ICI immunotherapy response in melanoma patients.

Elucidating the regulatory role of long non-coding RNAs in drought stress response during seed germination in leaf mustard.

Leaf mustard (Brassica juncea L. Czern & Coss), an important vegetable crop, experiences pronounced adversity due to seasonal drought stress, particularly at the seed germination stage. Although there is partial comprehension of drought-responsive genes, the role of long non-coding RNAs (lncRNAs) in adjusting mustard's drought stress response is largely unexplored. In this study, we showed that the drought-tolerant cultivar 'Weiliang' manifested a markedly lower base water potential (-1.073 MPa vs -0.437 MPa) and higher germination percentage (41.2% vs 0%) than the drought-susceptible cultivar 'Shuidong' under drought conditions. High throughput RNA sequencing techniques revealed a significant repertoire of lncRNAs from both cultivars during germination under drought stress, resulting in the identification of 2,087 differentially expressed lncRNAs (DELs) and their correspondingly linked 12,433 target genes. It was noted that 84 genes targeted by DEL exhibited enrichment in the photosynthesis pathway. Gene network construction showed that MSTRG.150397, a regulatory lncRNA, was inferred to potentially modulate key photosynthetic genes (Psb27, PetC, PetH, and PsbW), whilst MSTRG.107159 was indicated as an inhibitory regulator of six drought-responsive PIP genes. Further, weighted gene co-expression network analysis (WGCNA) corroborated the involvement of light intensity and stress response genes targeted by the identified DELs. The precision and regulatory impact of lncRNA were verified through qPCR. This study extends our knowledge of the regulatory mechanisms governing drought stress responses in mustard, which will help strategies to augment drought tolerance in this crop.

Long non-coding RNAs; potential contributors in cancer chemoresistance through modulating diverse molecular mechanisms and signaling pathways.

One of the mainstays of cancer treatment is chemotherapy. Drug resistance, however, continues to be the primary factor behind clinical treatment failure. Gene expression is regulated by long non-coding RNAs (lncRNAs) in several ways, including chromatin remodeling, translation, epigenetic, and transcriptional levels. Cancer hallmarks such as DNA damage, metastasis, immunological evasion, cell stemness, drug resistance, metabolic reprogramming, and angiogenesis are all influenced by LncRNAs. Numerous studies have been conducted on LncRNA-driven mechanisms of resistance to different antineoplastic drugs. Diverse medication kinds elicit diverse resistance mechanisms, and each mechanism may have multiple contributing factors. As a result, several lncRNAs have been identified as new biomarkers and therapeutic targets for identifying and managing cancers. This compels us to thoroughly outline the crucial roles that lncRNAs play in drug resistance. In this regard, this article provides an in-depth analysis of the recently discovered functions of lncRNAs in the pathogenesis and chemoresistance of cancer. As a result, the current research might offer a substantial foundation for future drug resistance-conquering strategies that target lncRNAs in cancer therapies.

Long non-coding RNA-mediated modulation of endoplasmic reticulum stress under pathological conditions.

Endoplasmic reticulum (ER) stress, which ensues from an overwhelming protein folding capacity, activates the unfolded protein response (UPR) in an effort to restore cellular homeostasis. As ER stress is associated with numerous diseases, it is highly important to delineate the molecular mechanisms governing the ER stress to gain insight into the disease pathology. Long non-coding RNAs, transcripts with a length of over 200 nucleotides that do not code for proteins, interact with proteins and nucleic acids, fine-tuning the UPR to restore ER homeostasis via various modes of actions. Dysregulation of specific lncRNAs is implicated in the progression of ER stress-related diseases, presenting these molecules as promising therapeutic targets. The comprehensive analysis underscores the importance of understanding the nuanced interplay between lncRNAs and ER stress for insights into disease mechanisms. Overall, this review consolidates current knowledge, identifies research gaps and offers a roadmap for future investigations into the multifaceted roles of lncRNAs in ER stress and associated diseases to shed light on their pivotal roles in the pathogenesis of related diseases.

Differential expression of long non-coding RNAs in colon cancer: Insights from transcriptomic analysis.

BACKGROUND: Colon Cancer (CC) incidence has sharply grown in recent years. Long non-coding RNAs (lncRNA) are produced by a group of non-protein-coding genes, and have important functions in controlling gene expression and impacting the biological features of various malignancies including CC. METHODS: Our research focused on examining the function of lncRNAs in the development of colon cancer. To this end, we selected and analyzed a dataset (GSE104836) from the GEO database, which contained information about the expression of mRNAs and lncRNAs in both colon cancer tissues and normal adjacent paired tumor tissues. The DESeq2 R package in Bioconductor was used to identify differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) that showed differences in expression levels. Next, by literature review of previous studies, we chose two lncRNAs (FENDRR and LINC00092) for additional studies. To validate our findings, a series of tests were performed on a total of 31 tumor tissues and normal paired adjacent tumor tissues. The lncRNA expression levels were assessed in tumor tissues as well as in surrounding normal tumor tissues. RESULTS: The data confirmed that just two particular lncRNAs, FENDRR and LINC00092, had considerably decreased expression levels throughout all stages of cancer. In addition, the survival assay was conducted using the GEPIA2 software, revealing that a reduced expression of FENDRR is correlated with a reduced overall survival. Furthermore, our investigation using receiver operating characteristic (ROC) methodology revealed that these two lncRNAs had significant discriminatory ability between colon cancer and normal tissues. To determine the cause of the decrease in the activity of these two long non-coding RNAs (lncRNAs), we used methylation-specific PCR (MSP) to examine the methylation pattern of their promoter regions. Our investigation revealed hypermethylation in the promoter regions of FENDRR and LINC00092 within tumor tissues compared to normal adjacent tumor tissues. CONCLUSION: Taken together, our findings revealed the lncRNAs signatures as potential therapeutic targets and molecular diagnostic biomarkers in colon cancer. Furthermore, the evidence provided substantiates the important role of promoter methylation in regulating the expression levels for both of these lncRNAs.