The role of microRNAs in hepatocarcinogenesis: current knowledge and future prospects

Otsuka, Motoyuki; Kishikawa, Takahiro; Yoshikawa, Takeshi; Ohno, Motoko; Takata, Akemi; Shibata, Chikako; Koike, Kazuhiko

doi:10.1007/s00535-013-0909-8

Cited by 32 publications

(30 citation statements)

References 139 publications

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“…Interestingly, in vitro and in vivo studies demonstrated that mi-RNAs such as miR-194, or miR-124 and miR-134, mediate to a significant extent the antitumorigenic effects of HNF1a and HNF4a, respectively [178,190,211]. Together, these studies support the potential of mi-RNA-based therapies in chronic liver disease and cancer, either by reactivating the expression of master regulators of mature liver phenotype or by mimicking their effects [212]. Nevertheless, many important issues need to be solved before a safe and efficacious application of these mi-RNA therapies can be implemented, including a comprehensive knowledge of all potential targets of the mi-RNA to be overexpressed or downregulated to avoid unwanted effects.…”

Section: Translational Perspectivessupporting

confidence: 51%

Regulation of hepatocyte identity and quiescence

Berasain

Avila

2015

Cell. Mol. Life Sci.

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The liver is a highly differentiated organ with a central role in metabolism, detoxification and systemic homeostasis. To perform its multiple tasks, liver parenchymal cells, the hepatocytes, express a large complement of enabling genes defining their complex phenotype. This phenotype is progressively acquired during fetal development and needs to be maintained in adulthood to guarantee the individual's survival. Upon injury or loss of functional mass, the liver displays an extraordinary regenerative response, mainly based on the proliferation of hepatocytes which otherwise are long-lived quiescent cells. Increasing observations suggest that loss of hepatocellular differentiation and quiescence underlie liver malfunction in chronic liver disease and pave the way for hepatocellular carcinoma development. Here, we briefly review the essential mechanisms leading to the acquisition of liver maturity. We also identify the key molecular factors involved in the preservation of hepatocellular homeostasis and finally discuss potential strategies to preserve liver identity and function.

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Section: Translational Perspectivessupporting

confidence: 51%

Regulation of hepatocyte identity and quiescence

Berasain

Avila

2015

Cell. Mol. Life Sci.

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“…A liverspecific miRNA, miR122, has been reported to be linked with pleiotropic physiological functions (Jopling, 2012;Otsuka et al, 2014), such as liver development, cholesterol metabolism, iron metabolism, and fatty acid metabolism (Takata et al, 2013a). A particularly intriguing function of miR122 is its role in promoting HCV replication (Jopling et al, 2005).…”

Section: Discussionmentioning

confidence: 98%

The flavonoid apigenin inhibits hepatitis C virus replication by decreasing mature microRNA122 levels

Shibata¹,

Ohno²,

Otsuka³

et al. 2014

Virology

Self Cite

106

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Despite recent progress in the development of direct-acting antivirals against hepatitis C virus (HCV), chronic HCV infection remains an important health burden worldwide. MicroRNA122 (miR122), a liver-specific microRNA (miRNA), positively regulates HCV replication, and systemic application of antisense oligonucleotides against miR122 led to the long-lasting suppression of HCV viremia in human clinical trials. Here, we report that apigenin, a flavonoid and an inhibitor of maturation of a subset of miRNAs, inhibits HCV replication in vitro. Apigenin decreased the expression levels of mature miR122 without significantly affecting cell growth. Because supplementation of synthesized miR122 oligonucleotides or overexpression of constitutively active TRBP blocked these effects, the inhibitory effects of apigenin on HCV replication seemed to be dependent on the reduction of mature miR122 expression levels through inhibition of TRBP phosphorylation. Thus, apigenin intake, either through regular diet or supplements, may decrease HCV replication in chronically infected patients.

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“…Accumulating evidence strongly suggests that aberrant microRNA (miRNA) expression is a common and important feature in human malignancies, facilitating proliferation, differentiation, apoptosis, invasion, and resistance to chemotherapeutic agents [5][6][7][8][9][10]. These reports strongly suggest the potential of miRNAs as biomarkers for cancer diagnosis and therapy [11,12].…”

Section: Introductionmentioning

confidence: 99%

Elevated miR-483-3p expression is an early event and indicates poor prognosis in pancreatic ductal adenocarcinoma

Wang

Sun

et al. 2015

Tumor Biol.

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MiR-483-3p has been reported to be widely involved in diverse human malignancies. However, the exact role of miR-483-3p remains elusive in pancreatic ductal adenocarcinoma (PDAC). The objective of this study is to determine the expression pattern and clinical implications of miR-483-3p in PDAC. MiR-483-3p levels were evaluated by locked nucleic acid-in situ hybridization (LNA-ISH) in a tissue microarray including 63 PDAC tumors and 10 normal pancreatic tissues, followed by evaluation in an independent set of 117 pairs of matched PDAC tumors and adjacent tumor-free pancreatic tissues. Expression of miR-483-3p was further evaluated in pancreatic intra-epithelial neoplasias (PanINs) and chronic pancreatitis (CP). The impact of miR-483-3p on cell proliferation, growth, and anchorage-independent colony formation was also assessed in vitro and in vivo. Microarray analysis revealed that miR-483-3p was positively stained in 61 (96.8 %) PDAC samples, but not detectable in normal pancreatic duct tissue. In the 117 PDAC samples, 100 % were miR-483-3p positive, with 55.6 % (65/117) strongly positive, compared to only 13.7 % (16/117) weakly positive in adjacent normal pancreatic duct tissues. MiR-483-3p expression was associated with tumor grading (p < 0.05) and was an independent predictor of poor overall survival in multivariate analysis (HR = 2.584; 95 % CI = 1.268-5.264). Moreover, from PanIN1 to PanIN3, the rate of strong miR-483-3p-positive staining was 0 % (0/39), 14.8 % (4/27), and 87.5 % (14/16), respectively. Six (54.5 %) CP samples were only weakly stained for miR-483-3p. Inhibition of miR-483-3p suppressed cell proliferation, growth, and colony formation in vitro and decreased tumor cell growth in nude mouse xenografts in vivo. These results suggest that aberrant miR-483-3p expression is an early event in PDAC tumorigenesis and is associated with tumor differentiation and prognosis. It also may be a potential target for PDAC molecular therapeutics.

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The role of microRNAs in hepatocarcinogenesis: current knowledge and future prospects

Cited by 32 publications

References 139 publications

Regulation of hepatocyte identity and quiescence

Regulation of hepatocyte identity and quiescence

The flavonoid apigenin inhibits hepatitis C virus replication by decreasing mature microRNA122 levels

Elevated miR-483-3p expression is an early event and indicates poor prognosis in pancreatic ductal adenocarcinoma

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