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Epigenetic repression of miR-132 expression by the hepatitis B virus x protein in hepatitis B virus-related hepatocellular carcinoma.
Cell Signal. 2013 May; 25(5):1037-43.CS

Abstract

Hepatitis B virus x (HBx) protein is involved in the initiation and progression of HBV-related hepatocellular carcinoma (HCC) by regulating host protein-coding genes. However, the role of HBx in the epigenetic repression of miRNAs, which play important roles in gene regulation during hepatocarcinogenesis, remains largely unknown. In this study, the expression of miR-132 in HCC cells, HBV-related HCC tissues, and serum were determined using real-time PCR. The level of DNA methylation on the promoter of miR-132 was examined using methylation-specific PCR (MSP). MiR-132 was functionally characterized in HCC cells with transiently altered miR-132 expression. HBx-induced DNA hypermethylation of the promoter of miR-132 was found to be more prevalent in HBx-expressing HepG2 cells than in control cells. Consistently, MiR-132 expression was also more frequently down-regulated in HBV-related HCC tissues than in adjacent noncancerous hepatic tissues and had a significant inverse correlation with HBx expression in HBV-related HCCs. Serum miR-132 levels were found to be significantly correlated with levels in tumor tissue. Finally, proliferation and colony formation of HCC cells were found to be suppressed by miR-132-mediated inhibition of the Akt-signaling pathway in miR132 transfected cells. Our study has demonstrated the epigenetic repression of miR-132 expression through DNA methylation induced by HBx. This work provides novel mechanistic insights into HBV-mediated hepatocarcinogenesis and suggests that miR-132 may be a promising biochemical marker and may have therapeutic applications in HBV-related HCC.

Authors+Show Affiliations

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23376496

Citation

Wei, Xufu, et al. "Epigenetic Repression of miR-132 Expression By the Hepatitis B Virus X Protein in Hepatitis B Virus-related Hepatocellular Carcinoma." Cellular Signalling, vol. 25, no. 5, 2013, pp. 1037-43.
Wei X, Tan C, Tang C, et al. Epigenetic repression of miR-132 expression by the hepatitis B virus x protein in hepatitis B virus-related hepatocellular carcinoma. Cell Signal. 2013;25(5):1037-43.
Wei, X., Tan, C., Tang, C., Ren, G., Xiang, T., Qiu, Z., Liu, R., & Wu, Z. (2013). Epigenetic repression of miR-132 expression by the hepatitis B virus x protein in hepatitis B virus-related hepatocellular carcinoma. Cellular Signalling, 25(5), 1037-43. https://doi.org/10.1016/j.cellsig.2013.01.019
Wei X, et al. Epigenetic Repression of miR-132 Expression By the Hepatitis B Virus X Protein in Hepatitis B Virus-related Hepatocellular Carcinoma. Cell Signal. 2013;25(5):1037-43. PubMed PMID: 23376496.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Epigenetic repression of miR-132 expression by the hepatitis B virus x protein in hepatitis B virus-related hepatocellular carcinoma. AU - Wei,Xufu, AU - Tan,Cui, AU - Tang,Chengyong, AU - Ren,Guosheng, AU - Xiang,Tingxiu, AU - Qiu,Zhu, AU - Liu,Rui, AU - Wu,Zhongjun, Y1 - 2013/01/30/ PY - 2012/11/21/received PY - 2013/01/08/revised PY - 2013/01/23/accepted PY - 2013/2/5/entrez PY - 2013/2/5/pubmed PY - 2013/10/19/medline SP - 1037 EP - 43 JF - Cellular signalling JO - Cell. Signal. VL - 25 IS - 5 N2 - Hepatitis B virus x (HBx) protein is involved in the initiation and progression of HBV-related hepatocellular carcinoma (HCC) by regulating host protein-coding genes. However, the role of HBx in the epigenetic repression of miRNAs, which play important roles in gene regulation during hepatocarcinogenesis, remains largely unknown. In this study, the expression of miR-132 in HCC cells, HBV-related HCC tissues, and serum were determined using real-time PCR. The level of DNA methylation on the promoter of miR-132 was examined using methylation-specific PCR (MSP). MiR-132 was functionally characterized in HCC cells with transiently altered miR-132 expression. HBx-induced DNA hypermethylation of the promoter of miR-132 was found to be more prevalent in HBx-expressing HepG2 cells than in control cells. Consistently, MiR-132 expression was also more frequently down-regulated in HBV-related HCC tissues than in adjacent noncancerous hepatic tissues and had a significant inverse correlation with HBx expression in HBV-related HCCs. Serum miR-132 levels were found to be significantly correlated with levels in tumor tissue. Finally, proliferation and colony formation of HCC cells were found to be suppressed by miR-132-mediated inhibition of the Akt-signaling pathway in miR132 transfected cells. Our study has demonstrated the epigenetic repression of miR-132 expression through DNA methylation induced by HBx. This work provides novel mechanistic insights into HBV-mediated hepatocarcinogenesis and suggests that miR-132 may be a promising biochemical marker and may have therapeutic applications in HBV-related HCC. SN - 1873-3913 UR - https://www.unboundmedicine.com/medline/citation/23376496/Epigenetic_repression_of_miR_132_expression_by_the_hepatitis_B_virus_x_protein_in_hepatitis_B_virus_related_hepatocellular_carcinoma_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0898-6568(13)00030-2 DB - PRIME DP - Unbound Medicine ER -