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题目:: Hepatitis B virus X protein downregulates expression of the miR-16 family in malignant hepatocytes in vitro.
作者:: Wu(G),Yu(F),Xiao(Z),Xu(K),Xu(J),Tang(W),Wang(J),Song(E)
状态:: 发布时间2011-06-29 , 更新时间 2015-02-04
期刊:: Br J Cancer
摘要:: Hepatitis B virus X protein (HBx) is involved in the initiation and progression of hepatocellular carcinoma (HCC) by regulating the host protein-coding genes. In this study, we showed that HBx altered the expression of microRNAs (miRNAs) to promote proliferation and transformation in malignant hepatocytes in vitro.,miRNA microarray and quantitative reverse-transcription polymerase chain reactions (qRT-PCRs) were performed to identify miRNAs that were differentially regulated by HBx in HCC cells. Protein, mRNA, and miRNA expression analyses; cell cycle and apoptosis analyses; loss/gain-of-function analysis; and luciferase reporter assays were performed to delineate the consequences of miR-16 family repression in HepG2 cells.,Hepatitis B virus X protein induced widespread deregulation of miRNAs in HepG2 cells, and the downregulation of the miR-16 family was reproducible in HepG2, SK-HEP-1, and Huh7 cells. CCND1, a target of the miR-16 family, was derepressed by HBx in HepG2 cells. c-Myc mediated the HBx-induced repression of miR-15a/16 in HepG2 cells. Ectopically expressed miR-15a/16 suppressed the proliferation, clonogenicity, and anchorage-independent growth of HBx-expressing HepG2 cells by arresting them in the G1 phase and inducing apoptosis, whereas reduced expression of miR-16 accelerated the growth and cell-cycle progression of HepG2 cells.,Hepatitis B virus X protein altered the in vitro expression of miRNAs in host malignant hepatocytes, particularly downregulating the miR-16 family. Repression of miR-15a/16 is c-Myc mediated and is required for the HBx-induced transformation of HepG2 cells in vitro. Therefore, miR-16 family may serve as a therapeutic target for hepatitis B virus (HBV)-associated HCC.
语言:: eng
DOI:

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