Cargando…
Tumor suppressor micro RNA miR-145 and onco micro RNAs miR-21 and miR-222 expressions are differentially modulated by Hepatitis B virus X protein in malignant hepatocytes
BACKGROUND: Hepatitis B Virus (HBV) X protein (HBx) is known to be involved in the initiation and progression of hepatocellular carcinoma (HCC) through modulation of host gene response. Alterations in miRNA expressions are frequently noted in HCC. This study is aimed to examine the role of HBx prote...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190340/ https://www.ncbi.nlm.nih.gov/pubmed/25260533 http://dx.doi.org/10.1186/1471-2407-14-721 |
_version_ | 1782338488405852160 |
---|---|
author | Bandopadhyay, Manikankana Banerjee, Arup Sarkar, Neelakshi Panigrahi, Rajesh Datta, Sibnarayan Pal, Ananya Singh, Shivram Prasad Biswas, Avik Chakrabarti, Shekhar Chakravarty, Runu |
author_facet | Bandopadhyay, Manikankana Banerjee, Arup Sarkar, Neelakshi Panigrahi, Rajesh Datta, Sibnarayan Pal, Ananya Singh, Shivram Prasad Biswas, Avik Chakrabarti, Shekhar Chakravarty, Runu |
author_sort | Bandopadhyay, Manikankana |
collection | PubMed |
description | BACKGROUND: Hepatitis B Virus (HBV) X protein (HBx) is known to be involved in the initiation and progression of hepatocellular carcinoma (HCC) through modulation of host gene response. Alterations in miRNA expressions are frequently noted in HCC. This study is aimed to examine the role of HBx protein in the modulation of oncogenic miRNA-21, miRNA-222 and tumor suppressor miRNA-145 in malignant hepatocytes. METHODS: Expressions of miRNA-21, miRNA-222 and miRNA-145 were measured in HepG2 cells transfected with HBx-plasmid (genotype D) and with full length HBV genome (genotype D) and also in stably HBV producing HepG2.2.15 cells using real time PCR. Their target mRNAs and proteins - PTEN, p27 and MAP3K - were analyzed by real time PCR and western blot respectively. miRNA expressions were measured after HBx/D mRNA specific siRNA treatment. The expressions of these miRNAs were analyzed in liver cirrhosis and HCC patients also. RESULTS: The study revealed a down-regulation of miRNA-21 and miRNA-222 expressions in HBx transfected HepG2 cells, pUC-HBV 1.3 plasmid transfected HepG2 cells as well as in HepG2.2.15 cells. Down regulation of miRNA-21 and miRNA-222 expression was observed in patient serum samples. Down regulation of miRNA-145 expression was observed in HepG2 cells transiently transfected with HBx and pUC-HBV1.3 plasmid as well as in patient samples but the expression of miRNA-145 was increased in HepG2.2.15 cells. Target mRNA and protein expressions were modulated in HepG2 cells and in HepG2.2.15 cell line consistent with the modulation of miRNA expressions. CONCLUSION: Thus, HBx protein differentially modulated the expression of miRNAs. The study throws light into possible way by which HBx protein acts through microRNA and thereby regulates host functioning. It might suggest new therapeutic strategies against hepatic cancer. |
format | Online Article Text |
id | pubmed-4190340 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-41903402014-10-10 Tumor suppressor micro RNA miR-145 and onco micro RNAs miR-21 and miR-222 expressions are differentially modulated by Hepatitis B virus X protein in malignant hepatocytes Bandopadhyay, Manikankana Banerjee, Arup Sarkar, Neelakshi Panigrahi, Rajesh Datta, Sibnarayan Pal, Ananya Singh, Shivram Prasad Biswas, Avik Chakrabarti, Shekhar Chakravarty, Runu BMC Cancer Research Article BACKGROUND: Hepatitis B Virus (HBV) X protein (HBx) is known to be involved in the initiation and progression of hepatocellular carcinoma (HCC) through modulation of host gene response. Alterations in miRNA expressions are frequently noted in HCC. This study is aimed to examine the role of HBx protein in the modulation of oncogenic miRNA-21, miRNA-222 and tumor suppressor miRNA-145 in malignant hepatocytes. METHODS: Expressions of miRNA-21, miRNA-222 and miRNA-145 were measured in HepG2 cells transfected with HBx-plasmid (genotype D) and with full length HBV genome (genotype D) and also in stably HBV producing HepG2.2.15 cells using real time PCR. Their target mRNAs and proteins - PTEN, p27 and MAP3K - were analyzed by real time PCR and western blot respectively. miRNA expressions were measured after HBx/D mRNA specific siRNA treatment. The expressions of these miRNAs were analyzed in liver cirrhosis and HCC patients also. RESULTS: The study revealed a down-regulation of miRNA-21 and miRNA-222 expressions in HBx transfected HepG2 cells, pUC-HBV 1.3 plasmid transfected HepG2 cells as well as in HepG2.2.15 cells. Down regulation of miRNA-21 and miRNA-222 expression was observed in patient serum samples. Down regulation of miRNA-145 expression was observed in HepG2 cells transiently transfected with HBx and pUC-HBV1.3 plasmid as well as in patient samples but the expression of miRNA-145 was increased in HepG2.2.15 cells. Target mRNA and protein expressions were modulated in HepG2 cells and in HepG2.2.15 cell line consistent with the modulation of miRNA expressions. CONCLUSION: Thus, HBx protein differentially modulated the expression of miRNAs. The study throws light into possible way by which HBx protein acts through microRNA and thereby regulates host functioning. It might suggest new therapeutic strategies against hepatic cancer. BioMed Central 2014-09-26 /pmc/articles/PMC4190340/ /pubmed/25260533 http://dx.doi.org/10.1186/1471-2407-14-721 Text en © Bandopadhyay et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Bandopadhyay, Manikankana Banerjee, Arup Sarkar, Neelakshi Panigrahi, Rajesh Datta, Sibnarayan Pal, Ananya Singh, Shivram Prasad Biswas, Avik Chakrabarti, Shekhar Chakravarty, Runu Tumor suppressor micro RNA miR-145 and onco micro RNAs miR-21 and miR-222 expressions are differentially modulated by Hepatitis B virus X protein in malignant hepatocytes |
title | Tumor suppressor micro RNA miR-145 and onco micro RNAs miR-21 and miR-222 expressions are differentially modulated by Hepatitis B virus X protein in malignant hepatocytes |
title_full | Tumor suppressor micro RNA miR-145 and onco micro RNAs miR-21 and miR-222 expressions are differentially modulated by Hepatitis B virus X protein in malignant hepatocytes |
title_fullStr | Tumor suppressor micro RNA miR-145 and onco micro RNAs miR-21 and miR-222 expressions are differentially modulated by Hepatitis B virus X protein in malignant hepatocytes |
title_full_unstemmed | Tumor suppressor micro RNA miR-145 and onco micro RNAs miR-21 and miR-222 expressions are differentially modulated by Hepatitis B virus X protein in malignant hepatocytes |
title_short | Tumor suppressor micro RNA miR-145 and onco micro RNAs miR-21 and miR-222 expressions are differentially modulated by Hepatitis B virus X protein in malignant hepatocytes |
title_sort | tumor suppressor micro rna mir-145 and onco micro rnas mir-21 and mir-222 expressions are differentially modulated by hepatitis b virus x protein in malignant hepatocytes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190340/ https://www.ncbi.nlm.nih.gov/pubmed/25260533 http://dx.doi.org/10.1186/1471-2407-14-721 |
work_keys_str_mv | AT bandopadhyaymanikankana tumorsuppressormicrornamir145andoncomicrornasmir21andmir222expressionsaredifferentiallymodulatedbyhepatitisbvirusxproteininmalignanthepatocytes AT banerjeearup tumorsuppressormicrornamir145andoncomicrornasmir21andmir222expressionsaredifferentiallymodulatedbyhepatitisbvirusxproteininmalignanthepatocytes AT sarkarneelakshi tumorsuppressormicrornamir145andoncomicrornasmir21andmir222expressionsaredifferentiallymodulatedbyhepatitisbvirusxproteininmalignanthepatocytes AT panigrahirajesh tumorsuppressormicrornamir145andoncomicrornasmir21andmir222expressionsaredifferentiallymodulatedbyhepatitisbvirusxproteininmalignanthepatocytes AT dattasibnarayan tumorsuppressormicrornamir145andoncomicrornasmir21andmir222expressionsaredifferentiallymodulatedbyhepatitisbvirusxproteininmalignanthepatocytes AT palananya tumorsuppressormicrornamir145andoncomicrornasmir21andmir222expressionsaredifferentiallymodulatedbyhepatitisbvirusxproteininmalignanthepatocytes AT singhshivramprasad tumorsuppressormicrornamir145andoncomicrornasmir21andmir222expressionsaredifferentiallymodulatedbyhepatitisbvirusxproteininmalignanthepatocytes AT biswasavik tumorsuppressormicrornamir145andoncomicrornasmir21andmir222expressionsaredifferentiallymodulatedbyhepatitisbvirusxproteininmalignanthepatocytes AT chakrabartishekhar tumorsuppressormicrornamir145andoncomicrornasmir21andmir222expressionsaredifferentiallymodulatedbyhepatitisbvirusxproteininmalignanthepatocytes AT chakravartyrunu tumorsuppressormicrornamir145andoncomicrornasmir21andmir222expressionsaredifferentiallymodulatedbyhepatitisbvirusxproteininmalignanthepatocytes |