Expression and Clinical Significance of the Novel Long Noncoding RNA ZNF674-AS1 in Human Hepatocellular Carcinoma (original) (raw)
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Current Research Progress on Long Noncoding RNAs Associated with Hepatocellular Carcinoma
Analytical Cellular Pathology, 2019
Hepatocellular carcinoma (HCC) is the second leading cause of mortality among cancers. It has been found that long noncoding RNAs (lncRNAs) are involved in many human cancers, including liver cancer. It has been identified that carcinogenic and tumor-suppressing lncRNAs are associated with complex processes in liver cancer. These lncRNAs may participate in a variety of pathological and biological activities, such as cell proliferation, apoptosis, invasion, and metastasis. Here, we review the regulation and function of lncRNA in liver cancer and evaluate the potential of lncRNA as a new goal for liver cancer.
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.
Medical Journal of Viral Hepatitis
Background: Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related deaths globally. Long non-coding RNAs (lncRNAs) may be considered as potential markers for HCC. The aim of this study is to evaluate the diagnostic and prognostic value of lncRNA ZFAS1 in HCC patients. Materials and methods: The current study included 100 cirrhotic patients with HCC, in addition to 100 cirrhotic patients without HCC as control group. RNA extraction was performed for quantification of ZFAS1 expression by real-time quantitative polymerase chain reaction. Results: ZFAS1 gene expression was significantly elevated in HCC group of patients compared to non-HCC group. The ability to distinguish HCC from cirrhotic controls by ZFAS1 was determined to be 1.00 (95% CI:1.00-1.00). Comparison between the diagnostic performance of ZFAS1 and AFP in differentiating HCC on top of cirrhosis from cirrhosis without HCC showed that, at cutoff values ≥-4.65 ZFAS1 gene had 100 % specificity and 99% sensitivity while, AFP at cutoff value ≥ 9.4 ng/ml had 100 % specificity and 76% sensitivity. Comparison of AUC for the two parameters demonstrated a significantly higher AUC for ZFAS1 than for AFP (Difference = 0.168, P <0.001). No statistically significant correlation between ZFAS1gene and any HCC characteristic however, a statistically significant correlation between AFP level and sex , BCLC staging was found. Conclusions: lncRNA ZFAS1 is a good diagnostic marker for HCC in cirrhotic patients with high sensitivity and specificity value, however ZFAS1has no prognostic importance in patients with HCC.s
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.
Analysis of long noncoding RNA expression in hepatocellular carcinoma of different viral etiology
Journal of translational medicine, 2016
Dysregulation of long noncoding RNA (lncRNA) expression contributes to the pathogenesis of many human diseases, including liver diseases. Several lncRNAs have been reported to play a role in the development of hepatocellular carcinoma (HCC). However, most studies have analyzed lncRNAs only in hepatitis B virus (HBV)-related HCC or in a single group of HCC patients regardless of the viral etiology. To investigate whether lncRNAs are differentially expressed in HCC of different viral etiology, we profiled 101 disease-related lncRNAs, including 25 lncRNAs previously associated with HCC, in liver specimens obtained from well-characterized patients with HBV-, hepatitis C virus (HCV)-, or hepatitis D virus (HDV)-associated HCC. We identified eight novel HCC-related lncRNAs that were significantly dysregulated in HCC tissues compared to their surrounding non-tumorous tissues. Some of these lncRNAs were significantly dysregulated predominantly in one specific hepatitis virus-related HCC, in...
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.
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...
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.
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...