Non-coding RNAs In Hepatocellular Carcinoma Research Articles

Non-coding RNAs in hepatocellular carcinoma: molecular functions and pathological implications.

Hepatocellular carcinoma (HCC) is a leading lethal malignancy worldwide. However, the molecular mechanisms underlying liver carcinogenesis remain poorly understood. Over the past two decades, overwhelming evidence has demonstrated the regulatory roles of different classes of non-coding RNAs (ncRNAs) in liver carcinogenesis related to a number of aetiologies, including HBV, HCV and NAFLD. Among the ncRNAs, microRNAs, which belong to a distinct class of small ncRNAs, have been proven to play a crucial role in the post-transcriptional regulation of gene expression. Deregulation of microRNAs has been broadly implicated in the inactivation of tumour-suppressor genes and activation of oncogenes in HCC. Modern high-throughput sequencing analyses have unprecedentedly identified a very large number of non-coding transcripts. Divergent groups of long ncRNAs have been implicated in liver carcinogenesis through interactions with DNA, RNA or proteins. Overall, ncRNAs represent a burgeoning field of cancer research, and we are only beginning to understand the importance and complicity of the ncRNAs in liver carcinogenesis. In this Review, we summarize the common deregulation of small and long ncRNAs in human HCC. We also comprehensively review the pathological roles of ncRNAs in liver carcinogenesis, epithelial-to-mesenchymal transition and HCC metastasis and discuss the potential applications of ncRNAs as diagnostic tools and therapeutic targets in human HCC.

Therapeutic targeting of noncoding RNAs in hepatocellular carcinoma: Recent progress and future prospects.

Due to the high mortality rate and unsatisfactory treatment options available, hepatocellular carcinoma (HCC) remains one of the most common malignancies and a leading cause of cancer-associated mortality. Novel therapeutic targets for HCC are urgently required. Advanced RNA sequencing technology enables the identification of considerable amounts of noncoding RNAs (ncRNAs), including small noncoding RNAs and long noncoding RNAs, which exhibit no protein-coding activities. In this respect, ncRNAs and their regulatory processes are important factors in liver tumorigenesis. The present review focuses on the characteristics and biological roles of ncRNAs in HCC. Potential therapeutic applications of ncRNAs in HCC are also evaluated.

Long non-coding RNA CASC2 regulates cell biological behaviour through the MAPK signalling pathway in hepatocellular carcinoma.

Long non-coding RNAs have previously been demonstrated to play important roles in regulating human diseases, especially cancer. However, the biological functions and molecular mechanisms of long non-coding RNAs in hepatocellular carcinoma have not been extensively studied. The long non-coding RNA CASC2 (cancer susceptibility candidate 2) has been characterised as a tumour suppressor in endometrial cancer and gliomas. However, the role and function of CASC2 in hepatocellular carcinoma remain unknown. In this study, using quantitative real-time polymerase chain reaction, we confirmed that CASC2 expression was downregulated in 50 hepatocellular carcinoma cases (62%) and in hepatocellular carcinoma cell lines compared with the paired adjacent tissues and normal liver cells. In vitro experiments further demonstrated that overexpressed CASC2 decreased hepatocellular carcinoma cell proliferation, migration and invasion as well as promoted apoptosis via inactivating the mitogen-activated protein kinase signalling pathway. Our findings demonstrate that CASC2 could be a useful tumour suppressor factor and a promising therapeutic target for hepatocellular carcinoma.

Long non-coding RNAs in hepatocellular carcinoma: Potential roles and clinical implications.

Long non-coding RNAs (lncRNAs) are a subgroup of non-coding RNA transcripts greater than 200 nucleotides in length with little or no protein-coding potential. Emerging evidence indicates that lncRNAs may play important regulatory roles in the pathogenesis and progression of human cancers, including hepatocellular carcinoma (HCC). Certain lncRNAs may be used as diagnostic or prognostic markers for HCC, a serious malignancy with increasing morbidity and high mortality rates worldwide. Therefore, elucidating the functional roles of lncRNAs in tumors can contribute to a better understanding of the molecular mechanisms of HCC and may help in developing novel therapeutic targets. In this review, we summarize the recent progress regarding the functional roles of lncRNAs in HCC and explore their clinical implications as diagnostic or prognostic biomarkers and molecular therapeutic targets for HCC.

[Research advances in diagnostic and therapeutic application of long-chain non-coding RNAs in hepatocellular carcinoma].

In recent years, hepatocellular carcinoma (HCC) has become one of the serious health-threatening malignancies worldwide, and its incidence and mortality rates continue to rise. Hepatitis B (HBV) is moderately endemic in China, with enormous numbers of HBV-related HCC cases. Although serum alpha-fetoprotein (AFP) and ultrasound are the major diagnostic methods for HCC, they have limited application for screening out early or small HCC. The current management of HCC is based on tumor size and location, not on suppressing tumorigenesis, and therefore patients are often faced with low 5-year survival and high relapse rates. Recent studies have shown that long-chain non-coding RNAs (lncRNAs) are closely associated with HCC tumorigenesis, which may have considerable utility as new diagnostic marker and treatment target for HCC. Here, we review the application of lncRNAs in the diagnosis, metastasis, treatment, recurrence, and prognosis of HCC.

Abstract 3818: Deregulated long non-coding RNAs in hepatocellular carcinoma (HCC)

Abstract Background: 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). However, small sample sizes in previous studies limited statistical power to identify reliable lncRNA biomarkers associated with hepatocarcinogenesis. The potential impacts of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection on expression of lncRNAs are also unclear. MATERIALS & METHODS: In this study approved by the Institutional Review Board of Columbia University Medical Center, 65 paired HCC tumor and adjacent non-tumor tissues were collected by the Center for Liver Disease and Transplantation of the Herbert Irving Comprehensive Cancer Center. We determined the expression profiles of 90 lncRNAs, 5 housekeeping gene reference controls and one negative control using the LncProfiler™ lncRNA qPCR array (System Biosciences). RESULTS: We found that eight lncRNAs (L1PA16, lincRNA-VLDLR, LUST, Zeb2NAT, MEG9, ncR-uPAR, p53 mRNA and TEA ncRNAs family) were significantly down-regulated in HCC tumor compared to non-tumor tissues. The fold changes ranged from -2.2 to -5.9. Four lncRNAs (H19, HOTAIR, HULC and MALAT1) previously associated with HCC were also up-regulated in tumor tissue, but did not reach statistical significance. We observed over 83% of the tumor tissues carrying one of those aberrant lncRNAs, indicating the importance of lncRNAs in HCC. Categorized by hepatitis infection, we observed that five lncRNAs were significantly repressed in HBV positive/HCV negative tumors (N = 13 pairs). No significantly aberrant lncRNA was observed in HCV positive/HBV negative tumors (N = 19) in comparison with non-tumor tissues. Within non-tumor tissues, we found 3 up-regulated lncRNAs (Kcnq1ot1, PSF inhibiting RNA and NRON) were significantly associated with HBV infection, and upregulated PRINS was significantly associated with HCV infection in comparison with viral negative cases. These data suggest that the deregulated lncRNAs found within HCC non-tumor tissues may be specifically modified by relevant hepatitis viral infection. CONCLUSIONS: Aberrant lncRNAs are potential HCC tumor biomarkers that are impacted by HBV or HCV infection. Further investigation of tumor specific biomarkers should consider the effects of different etiologies that will improve early detection of HCC. Citation Format: Jing Shen, Abby B. Siegel, Helen Remotti, Qiao Wang, Yueyue Shen, Regina M. Santella. Deregulated long non-coding RNAs in hepatocellular carcinoma (HCC). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3818. doi:10.1158/1538-7445.AM2015-3818

Long noncoding RNAs in hepatocellular carcinoma: Novel insights into their mechanism.

Hepatocellular carcinoma (HCC) is the predominant subject of liver malignancies which arouse global concern. Advanced studies have found that long noncoding RNAs (lncRNAs) are differentially expressed in HCC and implicate they may play distinct roles in the pathogenesis and metastasis of HCC. However, the underlying mechanisms remain largely unclear. In this review, we summarized the functions and mechanisms of those known aberrantly expressed lncRNAs identified in human HCC tissues. We hope to enlighten more comprehensive researches on the detailed mechanisms of lncRNAs and their application in clinic, such as being used as diagnostic and prognostic biomarkers and the targets for potential therapy. Although studies on lncRNAs in HCC are still deficient, an improved understanding of the roles played by lncRNAs in HCC will lead to a much more effective utilization of those lncRNAs as novel candidates in early detection, diagnosis, prevention and treatment of HCC.

Role of long noncoding RNAs in hepatocellular carcinoma

Role of long noncoding RNAs in hepatocellular carcinoma

The role of noncoding RNA in hepatocellular carcinoma.

Increasing noncoding RNAs (ncRNAs) were found to show abnormal expression patterns in various human cancers. Based on their length, ncRNAs are briefly divided into two categories. Transcripts that are shorter than 200 nucleotides are recognized as short/small noncoding RNAs and greater than 200 nucleotides as long noncoding RNAs (lncRNAs). Short/small noncoding RNAs include microRNAs, piRNAs, snoRNAs, and endogenous siRNAs. Numerous studies have revealed that these short/small ncRNA play important roles in multiple biological processes and tumorigenesis. In contrast to small ncRNAs, long noncoding RNAs are much less known concerning their functions in human cancers especially in hepatocellular carcinoma (HCC). In this review, we highlight recent progress regarding HCC development, tumorigenesis, metastasis, clinical implication, as well as the role in the risk of HBV infection.

Deep sequencing of small RNA transcriptome reveals novel non-coding RNAs in hepatocellular carcinoma

Small non-coding RNAs (ncRNA) are increasingly recognized to play important roles in tumorigenesis. With the advent of deep sequencing, efforts have been put forth to profile the miRNome in a number of human malignancies. However, information on ncRNA in hepatocellular carcinoma (HCC), especially the non-microRNA transcripts, is still lacking. Small RNA transcriptomes of two HCC cell lines (HKCI-4 and HKCI-8) and an immortalized hepatocyte line (MIHA) were examined using Illumina massively parallel sequencing. Dysregulated ncRNAs were verified in paired HCC tumors and non-tumoral livers (n=73) by quantitative reverse transcription-polymerase chain reaction. Clinicopathologic correlations and in vitro functional investigations were further carried out. The combined bioinformatic and biological analyses showed the presence of ncRNAs and the involvement of a new PIWI-interacting RNA (piRNA), piR-Hep1, in liver tumorigenesis. piR-Hep1 was found to be upregulated in 46.6% of HCC tumors compared to the corresponding adjacent non-tumoral liver. Silencing of piR-Hep1 inhibited cell viability, motility, and invasiveness, with a concomitant reduction in the level of active AKT phosphorylation. In the analysis of miRNA, we showed for the first time, the abundant expression of miR-1323 in HCC and its distinct association in tumors arising from a cirrhotic background. Furthermore, miR-1323 overexpression in cirrhotic HCC correlated with poorer disease-free and overall survivals of patients (p<0.009). Our study demonstrated the value of next-generation sequencing in dissecting the ncRNome in cancer. The comprehensive definition of transcriptome unveils virtually all types of ncRNAs and provides new insight into liver carcinogenetic events.