MicroRNAs in Hepatocellular Carcinoma: Regulation, Function, and Clinical Implications

Sun, Jie; Lu, Haiqi; Wang, Liangjing; Jin, Hongchuan

doi:10.1155/2013/924206

Cited by 70 publications

(61 citation statements)

References 194 publications

(123 reference statements)

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“…PTEN is also implicated in HCV-associated HCC, where miR-21 overexpression was observed. 115 Importantly, this miRNA was evidenced to directly target PTEN mRNA, 116 therefore favoring telomerase activity directly and indirectly, 117 as already mentioned. Furthermore, miR-21 overexpression reduces the function of SPRY2 mRNA (another validated target of this miRNA), which was shown to up-regulate PTEN.…”

Section: Non-coding Rnas In Telomerase Regulation By Oncogenic Virusesmentioning

confidence: 59%

Tumor Cell Development: A Role for Viruses and Telomerase Activity?

2014

Advances in Tumor Virology

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ABSTRACT:Telomere biology is an important aspect of human cancer, because the telomere dysfunction and telomerase activity are associated with genomic instability and cellular immortalization. In this article, we review the regulation of telomere dynamics and telomerase activity in virus-related cancers. Viruses may exploit these events to favor its replication and, therefore, may differ from non-viral cancers in this regard. Focusing on Epstein-Barr virus (EBV), human papillomavirus (HPV), hepatitis B virus (HBV), and hepatitis C virus (HCV), which concentrate the majority of the evidence regarding telomere biology and viral cancers), although other viruses are more briefly mentioned, it is noticeable that regulatory mechanisms of telomere dynamics and telomerase activity are virus specific. Such mechanisms include accelerated telomere shortening because of higher rates of cellular proliferation, telomerase activity regulation, and activation of alternative lengthening of telomeres (ALT). Additionally, there is also some evidence supporting a role of viral noncoding RNAs (ncRNAs) and virus-induced alterations in host ncRNAs in telomerase activity. Clarification of the roles of telomere biology in mediating viral cancers would have implications only for developing telomere-targeting anti-cancer approaches and, possibly, to accelerate advances in other telomererelated diseases, such as non-viral cancers and other aging traits.

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Section: Non-coding Rnas In Telomerase Regulation By Oncogenic Virusesmentioning

confidence: 59%

Tumor Cell Development: A Role for Viruses and Telomerase Activity?

2014

Advances in Tumor Virology

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“…Various miRNAs are oncogenic in HCC, including miR-21, miR-221, miR-222 and miR-151; however it has been suggested that a number of miRNAs, including miR-29, miR-122, miR-125b, miR-101 and miR-139, may be tumor suppressive in HCC (17). It has previously been demonstrated that in HCC, miRNAs are involved in the regulation of cell survival and proliferation, angiogenesis and metastasis (9,17).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies investigating HCC have demonstrated that miRNA expression profiles are signatures of HCC development and progression (6)(7)(8). Various miRNAs, including miR-302d, have been implicated in the onset and development of HCC (9). The identification of novel functions of specific miRNAs may help elucidate the molecular mechanisms that underlie HCC development and progression.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-302d downregulates TGFBR2 expression and promotes hepatocellular carcinoma growth and invasion

Chen

Guo

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Hepatocellular carcinoma (HCC) is the second leading cause of cancer-associated mortality in China and the third leading cause worldwide. A number of microRNAs (miRNAs) have been implicated in cell cycle progression, growth, apoptosis, angiogenesis and metastasis in HCC. In the present study, reverse transcription-quantitative polymerase chain reaction analysis was used to detect the levels of miR-302d expression in the tissues of 30 patients with HCC. Cell cycle, growth, apoptosis and migration were analyzed using a cell counting kit, flow cytometry and a Transwell migration assay. Dual-luciferase reporter assays and western blotting were also used to analyze the expression levels of transforming growth factor beta type II receptor (TGFBR2) in HCC cells. The present study evaluated the role of miR-302d in the development and progression of HCC. Abnormally high expression of miR-302d was observed in 80% of HCC specimens. Moreover, patients with lower levels of miR-302d expression experienced a longer survival time than those with higher levels of miR-302d expression. It was demonstrated that miR-302d promoted HCC cell growth and migration, suppressed cell apoptosis and affected cell cycle distribution in vitro, and augmented tumorigenicity in vivo. Furthermore, TGFBR2, which is a tumor suppressor, was confirmed as a target of miR-302d in HCC cells. Dual-luciferase reporter assays indicated that TGFBR2 expression was negatively regulated by miR-302d. Taken together, the results of the present study suggest that miR-302d may serve as a valuable tool for predicting the prognosis of patients with HCC.

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“…15e17 Recent studies have demonstrated that miRNAs are important in OC activation and development of hepatocellular carcinoma (HCC). 18,19 HCC represents 90% of primary liver cancers, it has poor prognosis, and its incidence is increasing worldwide. 20 A study from Gailhouste et al 21 identified direct targeting of DNA methyltransferase 1 by the hepatospecific miR-148a (down-regulated in HCC patients, mouse, and human HCC cell lines) to be critical for hepatic differentiation.…”

mentioning

confidence: 99%

“…miRNA expression is dysregulated in various types of cancer, including HCC. 19,22,23 The miR-133 family (miR-133a-1, miR-133a-2, and miR133b) is among the most studied miRNAs. 24 These miRNAs are transcribed as bicistronic RNAs together with miR-1-2, miR-1-1, and miR-206, respectively.…”

mentioning

confidence: 99%

miR-133b Regulation of Connective Tissue Growth Factor

Gjymishka

et al. 2016

The American Journal of Pathology

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miRNAs are involved in liver regeneration, and their expression is dysregulated in hepatocellular carcinoma (HCC). Connective tissue growth factor (CTGF), a direct target of miR-133b, is crucial in the ductular reaction (DR)/oval cell (OC) response for generating new hepatocyte lineages during liver injury in the context of hepatotoxin-inhibited hepatocyte proliferation. Herein, we investigate whether miR-133b regulation of CTGF influences HCC cell proliferation and migration, and DR/OC response. We analyzed miR133b expression and found it to be down-regulated in HCC patient samples and induced in the rat DR/OC activation model of 2-acetylaminofluorene with partial hepatectomy. Furthermore, overexpression of miR-133b via adenoviral system in vitro led to decreased CTGF expression and reduced proliferation and Transwell migration of both HepG2 HCC cells and WBF-344 rat OCs. In vivo, overexpression of miR133b in DR/OC activation models of 2-acetylaminofluorene with partial hepatectomy in rats, and 3,5-diethoxycarbonyl-1,4-dihydrocollidine in mice, led to down-regulation of CTGF expression and OC proliferation. Collectively, these results show that miR-133b regulation of CTGF is a novel mechanism critical for the proliferation and migration of HCC cells and OC response. (Am J Pathol 2016 http://dx

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MicroRNAs in Hepatocellular Carcinoma: Regulation, Function, and Clinical Implications

Cited by 70 publications

References 194 publications

Tumor Cell Development: A Role for Viruses and Telomerase Activity?

Tumor Cell Development: A Role for Viruses and Telomerase Activity?

MicroRNA-302d downregulates TGFBR2 expression and promotes hepatocellular carcinoma growth and invasion

miR-133b Regulation of Connective Tissue Growth Factor

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