Current Research Progress on Long Noncoding RNAs Associated with Hepatocellular Carcinoma (original) (raw)
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Long Noncoding RNAs as a Key Player in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is a major malignancy in the liver and has emerged as one of the main cancers in the world with a high mortality rate. However, the molecular mechanisms of HCC are still poorly understood. Long noncoding RNAs (lncRNAs) have recently come to the forefront as functional non–protein-coding RNAs that are involved in a variety of cellular processes ranging from maintaining the structural integrity of chromosomes to gene expression regulation in a spatiotemporal manner. Many recent studies have reported the involvement of lncRNAs in HCC which has led to a better understanding of the underlying molecular mechanisms operating in HCC. Long noncoding RNAs have been shown to regulate development and progression of HCC, and thus, lncRNAs have both diagnostic and therapeutic potentials. In this review, we present an overview of the lncRNAs involved in different stages of HCC and their potential in clinical applications which have been studied so far.
The Role of Long Non-Coding RNAs in Hepatocarcinogenesis
International Journal of Molecular Sciences
Whole-transcriptome analyses have revealed that a large proportion of the human genome is transcribed in non-protein-coding transcripts, designated as long non-coding RNAs (lncRNAs). Rather than being "transcriptional noise", increasing evidence indicates that lncRNAs are key players in the regulation of many biological processes, including transcription, post-translational modification and inhibition and chromatin remodeling. Indeed, lncRNAs are widely dysregulated in human cancers, including hepatocellular carcinoma (HCC). Functional studies are beginning to provide insights into the role of oncogenic and tumor suppressive lncRNAs in the regulation of cell proliferation and motility, as well as oncogenic and metastatic potential in HCC. A better understanding of the molecular mechanisms and the complex network of interactions in which lncRNAs are involved could reveal novel diagnostic and prognostic biomarkers. Crucially, it may provide novel therapeutic opportunities to add to the currently limited number of therapeutic options for HCC patients. In this review, we summarize the current status of the field, with a focus on the best characterized dysregulated lncRNAs in HCC.
Behind the curtain of non-coding RNAs; long non-coding RNAs regulating hepatocarcinogenesis
World Journal of Gastroenterology
Hepatocellular carcinoma (HCC) is one of the most common and aggressive cancers worldwide. HCC is the fifth common malignancy in the world and the second leading cause of cancer death in Asia. Long non-coding RNAs (lncRNAs) are RNAs with a length greater than 200 nucleotides that do not encode proteins. lncRNAs can regulate gene expression and protein synthesis in several ways by interacting with DNA, RNA and proteins in a sequence specific manner. They could regulate cellular and developmental processes through either gene inhibition or gene activation. Many studies have shown that dysregulation of lncRNAs is related to many human diseases such as cardiovascular diseases, genetic disorders, neurological diseases, immune mediated disorders and cancers. However, the study of lncRNAs is challenging as they are poorly conserved between species, their expression levels aren't as high as that of mRNAs and have great interpatient variations. The study of lncRNAs expression in cancers have been a breakthrough as it unveils potential biomarkers and drug targets for cancer therapy and helps understand the mechanism of pathogenesis. This review discusses many long non-coding RNAs and their contribution in HCC, their role in development, metastasis, and prognosis of HCC and how to regulate and target these lncRNAs as a therapeutic tool in HCC treatment in the future.
The Landscape of lncRNAs in Hepatocellular Carcinoma: A Translational Perspective
Cancers, 2021
LncRNAs are emerging as relevant regulators of multiple cellular processes involved in cell physiology as well as in the development and progression of human diseases, most notably, cancer. Hepatocellular carcinoma (HCC) is a prominent cause of cancer-related death worldwide due to the high prevalence of causative factors, usual cirrhotic status of the tumor-harboring livers and the suboptimal benefit of locoregional and systemic therapies. Despite huge progress in the molecular characterization of HCC, no oncogenic loop addiction has been identified and most genetic alterations remain non-druggable, underscoring the importance of advancing research in novel approaches for HCC treatment. In this context, long non-coding RNAs (lncRNAs) appear as potentially useful targets as they often exhibit high tumor- and tissue-specific expression and many studies have reported an outstanding dysregulation of lncRNAs in HCC. However, there is a limited perspective of the potential role that dere...
Cancers, 2015
Long non-coding RNAs (lncRNAs) are larger than 200 nucleotides in length and pervasively expressed across the genome. An increasing number of studies indicate that lncRNA transcripts play integral regulatory roles in cellular growth, division, differentiation and apoptosis. Deregulated lncRNAs have been observed in a variety of human cancers, including hepatocellular carcinoma (HCC). We determined the expression profiles of 90 lncRNAs for 65 paired HCC tumor and adjacent non-tumor tissues, and 55 lncRNAs were expressed in over 90% of samples. Eight lncRNAs were significantly down-regulated in HCC tumor compared to non-tumor tissues (p < 0.05), but no lncRNA achieved statistical significance after Bonferroni correction for multiple comparisons. Within tumor tissues, carrying more aberrant lncRNAs (6-7) was associated with a borderline significant reduction Cancers 2015, 7 1848 in survival (HR = 8.5, 95% CI: 1.0-72.5). The predictive accuracy depicted by the AUC was 0.93 for HCC su...
Emerging role of lncRNA in cancer: a potential avenue in molecular medicine
Annals of Translational Medicine, 2016
Hepatocellular carcinoma (HCC) accounts for the second largest number of cancer related deaths globally with limited management options for the advanced disease. Although substantial research has identified molecular targets, with strong validation in pre-clinical in vivo studies, translation of therapeutics to clinics has shown modest success. In a recent manuscript in Hepatology, Zhou and Yang et al. unravel a novel p53 associated long noncoding RNA (PRAL) as a potential prognostic marker and molecular target in HCC. Their work provides a promising approach at capitalizing the tumor suppressive role of p53 protein in fighting HCC. More importantly, it emphasizes the evolving significance of long non-coding RNAs (lncRNA) in molecular medicine. Current research trends focus on identifying and understanding roles of lncRNA in regulation of gene expression relevant to multiple disease pathophysiologies thereby presenting a new avenue of research in molecular and translational medicine.
Cancers
Hepatocellular carcinoma (HCC) is a predominant malignancy with increasing incidences and mortalities worldwide. In Western countries, the progressive affirmation of Non-alcoholic Fatty Liver Disease (NAFLD) as the main chronic liver disorder in which HCC occurrence is appreciable even in non-cirrhotic stages, constitutes a real health emergency. In light of this, a further comprehension of molecular pathways supporting HCC onset and progression represents a current research challenge to achieve more tailored prognostic models and appropriate therapeutic approaches. RNA non-coding transcripts (ncRNAs) are involved in the regulation of several cancer-related processes, including HCC. When dysregulated, these molecules, conventionally classified as “small ncRNAs” (sncRNAs) and “long ncRNAs” (lncRNAs) have been reported to markedly influence HCC-related progression mechanisms. In this review, we describe the main dysregulated ncRNAs and the relative molecular pathways involved in HCC p...
Recurrently deregulated lncRNAs in hepatocellular carcinoma
Nature Communications, 2017
Hepatocellular carcinoma (HCC) cells often invade the portal venous system and subsequently develop into portal vein tumour thrombosis (PVTT). Long noncoding RNAs (lncRNAs) have been associated with HCC, but a comprehensive analysis of their specific association with HCC metastasis has not been conducted. Here, by analysing 60 clinical samples' RNA-seq data from 20 HCC patients, we have identified and characterized 8,603 candidate lncRNAs. The expression patterns of 917 recurrently deregulated lncRNAs are correlated with clinical data in a TCGA cohort and published liver cancer data. Matched array data from the 60 samples show that copy number variations (CNVs) and alterations in DNA methylation contribute to the observed recurrent deregulation of 235 lncRNAs. Many recurrently deregulated lncRNAs are enriched in co-expressed clusters of genes related to cell adhesion, immune response and metabolic processes. Candidate lncRNAs related to metastasis, such as HAND2-AS1, were further validated using RNAi-based loss-of-function assays. Thus, we provide a valuable resource of functional lncRNAs and biomarkers associated with HCC tumorigenesis and metastasis.
Oncotarget, 2016
Functional characterization of long non-coding RNAs (lncRNAs) and their pathological relevance is still a challenging task. Abnormal expression of a few long non-coding RNAs have been found associated with hepatocellular carcinoma, with potential implications to both improve our understanding of molecular mechanism of liver carcinogenesis and to discover biomarkers for early diagnosis or therapy. However, the understanding of the global role of lncRNAs during HCC development is still in its infancy. In this study, we produced RNA-Seq data from 23 liver tissues (controls, cirrhotic and HCCs) and applied statistical and gene network analysis approaches to identify and characterize expressed lncRNAs. We detected 5,525 lncRNAs across different tissue types and identified 57 differentially expressed lncRNAs in HCC compared with adjacent non-tumour tissues using stringent criteria (FDR<0.05, Fold Change>2). Using weighted gene co-expression network analysis (WGCNA), we found that di...
Long Noncoding RNAs in Interaction With RNA Binding Proteins in Hepatocellular Carcinoma
Hepatitis Monthly, 2014
Background: Gene expression microarrays' analyses provide a description of long noncoding RNAs (lncRNAs) with lack of coding protein function that is often important in human cancer. Objectives: A number of lncRNAs that have been well characterized in hepatocellular carcinoma (HCC) have been scheduled in this study to discuss for protein-lncRNA interaction. Materials and Methods: The identified lncRNAs were analyzed by bioinformatics tools, starBase and lncRNA db, to anticipate the RNAbinding proteins (RBPs) that tend to interact to HCC-related lncRNAs. The most important predicted RBPs in interaction with well-known lncRNAs in HCC were briefly discussed. Results: The lncRNAs HOTTIP, H19, HOTAIR, MALAT1, antisense Igf2r (AIR), HOXA13, GTL2 (also called MEG3) and uc002mb have been reported in association with HCC. Besides, this study predicted that eIF4AIII, PTB and FUS were the most involved RBPs in interaction with HCC-related lncRNAs. Conclusions: This information provides an explanation for the previously valuable literature on the functions of lncRNAs and suggest for the novel therapeutic targeting.