[新闻]B型肝炎病毒通过小分子RNA促进癌变的疾病

StephenW

Hepatitis B virus promotes oncogenesis through microRNA modulation
January 16, 2013 in Diseases, Conditions, Syndromes

Viruses prompt oncogenic transformation by genetically altering infected cells. Several recent studies have demonstrated that viruses alter the expression of microRNAs, non-coding RNA molecules that can block the expression of target genes.

In this issue of the Journal of Clinical Investigation, Xiaoje Xu and colleagues at the Beijing Institute of Biotechnology report that miR-148a is repressed by hepatitis B virus (HBV) X protein (HBx) to promote growth and metastasis of liver cancer. In normal liver cells, miR-148a represses the expression of the oncogenic protein HPIP, but the hepatitis B virus prevents expression of miR-148a, leading to increased levels of HPIP and subsequent oncogenic transformation. This study demonstrates that a cancer-associated virus promotes carcinogenesis through direct manipulation of a microRNA. More information: Hepatitis B virus X protein represses miRNA-148a to enhance tumorigenesis, Journal of Clinical Investigation, 2013. Journal reference: Journal of Clinical Investigation search and more info website Provided by Journal of Clinical Investigation

Read more at: http://medicalxpress.com/news/20 ... modulation.html#jCp

StephenW

B型肝炎病毒通过小分子RNA促进癌变的疾病

2013年1月16日

病毒提示通过基因改变病毒感染的细胞的恶性转化。最近的一些研究表明，病毒改变了表达的microRNA，非编码RNA分子，可以阻止靶基因的表达。



在这杂志发行临床研究，Xiaoje徐和他的同事在北京生物技术研究所的报告发现miR-148a的抑制乙型肝炎病毒（HBV）X蛋白（HBx蛋白）促进肝癌生长和转移的。在正常肝细胞中，miR-148a的抑制致癌蛋白的表达HPIP，但B型肝炎病毒阻止了miR-148a的表达，导致HPIP和随后的致癌转化水平的提高。这项研究表明，一个与癌症相关的病毒通过直接操纵的microRNA促进致癌。



了解更多：http://medicalxpress.com/news/2013-01-hepatitis-virus-oncogenesis-microrna-modulation.html＃JCP

咬牙硬挺

研究逐步深入

bigben446

http://www.ncbi.nlm.nih.gov/pubmed/23321675?dopt=Abstract

Title: Hepatitis B virus X protein represses miRNA-148a to enhance tumorigenesis
Author: Xu, X.; Fan, Z.; Kang, L. (...)
Source: J Clin Invest, 2013,
Abstract:
  MicroRNAs (miRNAs) have been shown to be dysregulated in virus-related cancers; however, miRNA regulation of virus-related cancer development and progression remains poorly understood. Here, we report that miR-148a is repressed by hepatitis B virus (HBV) X protein (HBx) to promote cancer growth and metastasis in a mouse model of hepatocellular carcinoma (HCC). Hematopoietic pre-B cell leukemia transcription factor-interacting protein (HPIP) is an important regulator of cancer cell growth. We used miRNA target prediction programs to identify miR-148a as a regulator of HPIP. Expression of miR-148a in hepatoma cells reduced HPIP expression, leading to repression of AKT and ERK and subsequent inhibition of mTOR through the AKT/ERK/FOXO4/ATF5 pathway. HBx has been shown to play a critical role in the molecular pathogenesis of HBV-related HCC. We found that HBx suppressed p53-mediated activation of miR-148a. Moreover,  expression of miR-148a was downregulated in patients with HBV-related liver cancer and negatively correlated with HPIP, which was upregulated in patients with liver cancer. In cultured cells and a mouse xenograft model, miR-148a reduced the growth, epithelial-to-mesenchymal transition, invasion, and metastasis of HBx-expressing hepatocarcinoma cells through inhibition of HPIP-mediated mTOR signaling. Thus, miR-148a activation or HPIP inhibition may be a useful strategy for cancer treatment.