Hepatitis C Virus Core Protein Down-Regulates p21Waf1/Cip1 and Inhibits Curcumin-Induced Apoptosis through MicroRNA-345 Targeting in Human Hepatoma Cells

Shiu, Tzu-Yue; Huang, Shih‐Ming; Shih, Yu‐Lueng; Chu, Heng-Cheng; Chang, Wei‐Kuo; Hsieh, Tsai‐Yuan

doi:10.1371/journal.pone.0061089

Cited by 38 publications

(22 citation statements)

References 43 publications

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“…HCC patients with multiple tumor nodes, venous infiltration and advanced TNM stage showed significantly higher levels of miR-345, which was consistent with poor prognosis prediction as reported by Jiang et al (14). Although great efforts have been put into the study of miR-345 on tumor cell growth, apoptosis and metastasis (7,8,(10)(11)(12)(13), the roles of miR-345 in the modulation of EMT process remain largely unelucidated in HCC. In our recent study, gain-and loss-of-function methods were used to determine the functional roles of miR-345 in EMT.…”

Section: Discussionsupporting

confidence: 76%

“…We suggest that the case number and etiology may be the causes of difference. HCV core protein upregulated the expression of miR-345 in HCC cells (13), while HBV infection is the main problem in China (22).…”

Section: Discussionmentioning

confidence: 99%

“…Rare studies reported the correlation between miR-345 and HCC. Shiu et al reported that hepatitis C virus (HCV) core protein upregulated the expression of miR-345, which inhibited curcumin-induced apoptosis by targeting p21 in Huh7 cells (13), and Jiang et al showed that HCC patients with good survival rates had high miR-345 expression level compared with that in cases with poor survival rates (14).…”

Section: Introductionmentioning

confidence: 99%

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miR-345 inhibits tumor metastasis and EMT by targeting IRF1-mediated mTOR/STAT3/AKT pathway in hepatocellular carcinoma

Xue

Wang

et al. 2017

International Journal of Oncology

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MicroRNAs (miRNAs) have been reported to play critical roles in tumor progression including hepatocellular carcinoma (HCC). Thus, the underlying mechanisms need further investigation. Previous study reported that loss of miR-345 expression indicated a poor prognosis of HCC patients. This study evaluated whether loss of miR-345 could promote the tumor metastasis and epithelial-mesenchymal-transition (EMT) of HCC by targeting interferon regulatory factor 1 (IRF1)-mediated mTOR/STAT3/AKT signaling. Underexpression of miR-345 was identified in 65 cases of human HCC compared to matched tumor-adjacent tissues by qRT-PCR. Moreover, we found that reduced expression of mi-345 was observed in HCC cell lines. The restoration of miR-345 inhibited cell migration and invasion in HCCLM3 cells, while its loss facilitated the cell mobility of HepG2 cells. Furthermore, miR-345 over-expression reduced lung metastases of HCC cells in nude mice. Notably, miR-345 overexpression prohibited, while its knockdown enhanced the EMT process of HCC cell lines in vitro. Bioinformatics software predicted that IRF1 was a direct target of miR-345. We then observed the negative regulation of miR-345 on IRF1 protein expression and the direct binding between them was further verified by dual-luciferase assays in HCC cells. In addition, over-expression of IRF1 mRNA was inversely correlated with the level of miR-345 in HCC specimens. Restoration of IRF1 resulted in promoted EMT and cell mobility in miR-345 overexpressing HCCLM3 cells. It was found that mTOR/STAT3/AKT pathway and its downstream targets including Slug, Snail and Twist may be involved in IRF1 mediated EMT process. In conclusion, miR-345 acts as an inhibitor of EMT process in HCC cells by targeting IRF1 and this study highlights the potential effects of miR-345 on prognosis and treatment of HCC.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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miR-345 inhibits tumor metastasis and EMT by targeting IRF1-mediated mTOR/STAT3/AKT pathway in hepatocellular carcinoma

Xue

Wang

et al. 2017

International Journal of Oncology

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“…An HCV core-induced Summary of the different studies that have analyzed the effect of HCV proteins on the host cell cycle. See text and references for details increase in the level of miR-345 was found to suppress endogenous p21 expression by targeting the 3′ untranslated region (UTR) of the p21 mRNA [ 117 ]. Decreases in the levels of p21 would lead to accelerated cell cycle progression, and increased p21 expression is frequently observed in human cancers [ 128 ].…”

Section: Hepatitis C Virus Modulates the G1/s Checkpointmentioning

confidence: 99%

Cell Cycle Regulation During Viral Infection

Bagga

Bouchard

2014

Methods in Molecular Biology

138

114

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To replicate their genomes in cells and generate new progeny, viruses typically require factors provided by the cells that they have infected. Subversion of the cellular machinery that controls replication of the infected host cell is a common activity of many viruses. Viruses employ different strategies to deregulate cell cycle checkpoint controls and modulate cell proliferation pathways. A number of DNA and RNA viruses encode proteins that target critical cell cycle regulators to achieve cellular conditions that are beneficial for viral replication. Many DNA viruses induce quiescent cells to enter the cell cycle; this is thought to increase pools of deoxynucleotides and thus, facilitate viral replication. In contrast, some viruses can arrest cells in a particular phase of the cell cycle that is favorable for replication of the specific virus. Cell cycle arrest may inhibit early cell death of infected cells, allow the cells to evade immune defenses, or help promote virus assembly. Although beneficial for the viral life cycle, virus-mediated alterations in normal cell cycle control mechanisms could have detrimental effects on cellular physiology and may ultimately contribute to pathologies associated with the viral infection, including cell transformation and cancer progression and maintenance. In this chapter, we summarize various strategies employed by DNA and RNA viruses to modulate the replication cycle of the virus-infected cell. When known, we describe how these virus-associated effects influence replication of the virus and contribute to diseases associated with infection by that specific virus.

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“…Although the effect did not appear specific to HCV infected carcinomas, Wong et al (2008) noted that downregulation of miR-223 in HCC tissue appeared to promote oncogenesis by disinhibiting the Stathmin 1/oncoprotein 18 (STMN-1) oncogene. An in vitro study in Huh 7 and HEK 293 human hepatoma cell lines demonstrated a likely HCV core protein induced upregulation of miR-345, which appeared to downregulate the p21 waf1/cip to promote carcinogenesis (Shiu et al, 2013). In another in vitro study of Huh 7.5 replicons, miR-491 was noted to both increase full genome HCV clones to replicate and to downregulate cell growth inhibition on the PI3K/Akt pathway (Ishida et al, 2011).…”

Section: Methodsmentioning

confidence: 99%

MicroRNA and hepatitis C virus- challenges in investigation and translation: a review of the literature

Waldron

Holodniy

2014

Diagnostic Microbiology and Infectious Disease

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Investigations into the role of microRNA (miRNA) in hepatitis C virus (HCV) infection, disease pathogenesis and host immune and treatment response have potential to produce innovations in diagnosis, prognosis and therapy. However, investigational challenges remain in generating clinically useful and reproducible results. We review the literature with a primary emphasis on methods and technologies used to construct our current understanding of miRNA and HCV disease. A second emphasis is to understand potential clinical research applications and provide clarification of previous study results. Many miRNA have key roles in viral and immunopathogenesis of HCV infection across multiple tissue compartments. Controversy exists among published studies regarding relative measurements, temporal changes and biological significance of specific miRNA and HCV infection. To reconcile diverging data, additional research into optimal sample processing, in vitro models, techniques for microarray differential expression of miRNAs, practices for sample result normalization, and effect of HCV genotype variation on expression are all necessary. Microarray and miRNA isolation techniques should be selected based on ability to generate reproducible results in the sample type of interest. More direct comparisons of efficacy and reliability of various multiplex microarrays and an improved consensus around miRNA normalization and quantitation are necessary so that data can be compared across studies.

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Hepatitis C Virus Core Protein Down-Regulates p21Waf1/Cip1 and Inhibits Curcumin-Induced Apoptosis through MicroRNA-345 Targeting in Human Hepatoma Cells

Cited by 38 publications

References 43 publications

miR-345 inhibits tumor metastasis and EMT by targeting IRF1-mediated mTOR/STAT3/AKT pathway in hepatocellular carcinoma

miR-345 inhibits tumor metastasis and EMT by targeting IRF1-mediated mTOR/STAT3/AKT pathway in hepatocellular carcinoma

Cell Cycle Regulation During Viral Infection

MicroRNA and hepatitis C virus- challenges in investigation and translation: a review of the literature

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