Upregulated MicroRNA-29a by Hepatitis B Virus X Protein Enhances Hepatoma Cell Migration by Targeting PTEN in Cell Culture Model

نویسندگان

  • Guangyao Kong
  • Junping Zhang
  • Shuai Zhang
  • Changliang Shan
  • Lihong Ye
  • Xiaodong Zhang
چکیده

Hepatitis B virus X protein (HBx) plays important roles in the development of hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) contribute to cancer development by acting as oncogenes or tumor suppressors. Previously, we reported that HBx was able to promote the migration of hepatoma HepG2 cells. However, the regulation of miRNAs in the development of HBV-related HCC is poorly understood. In the present study, we reported that miR-29a was a novel regulator of migration of hepatoma cells mediated by HBx. Our data showed that the expression of miR-29a was dramatically increased in p21-HBx transgenic mice, HBx-transfected hepatoma HepG2-X (or H7402-X) cells and HepG2.2.15 cells that constitutively replicate HBV. However, our data showed that miR-29a was upregulated in 4 of the 11 clinical HCC samples. We found that the overexpression of miR-29a promoted the migration of HepG2 cells, while a specific miR-29a inhibitor could partially abolish the enhanced migration of HepG2-X cells. Moreover, we identified PTEN was one of the target genes of miR-29a in HepG2 cells. The deletion of the miR-29a-binding site was able to abolish the role of miR-29a in suppression of luciferase activity of the PTEN 3'UTR reporter. Meanwhile, the overexpression of PTEN was able to reverse the promoted migration of HepG2 cells mediated by miR-29a. Moreover, our data showed that the modulation of Akt phosphorylation, a downstream factor of PTEN, was involved in the cell migration enhanced by miR-29a, suggesting that miR-29a is responsible for the cell migration through its target gene PTEN. Thus, we conclude that miR-29a is involved in the regulation of migration of hepatoma cells mediated by HBx through PTEN in cell culture model.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

microRNA-29a functions as a tumor suppressor in nasopharyngeal carcinoma 5-8F cells through targeting VEGF

Objective(s): microRNA-29 (miR-29) family miRNAs have been mentioned as tumor suppressive genes in several human cancers. The purpose of this study was to investigate the function of miR-29a in nasopharyngeal carcinoma (NPC) cells. Materials and Methods: Human NPC cell line 5-8F was transfected with mimic, inhibitor or scrambled controls...

متن کامل

miR-29a promotes hepatitis B virus replication and expression by targeting SMARCE1 in hepatoma carcinoma

AIM To investigate the functional role and underlying molecular mechanism of miR-29a in hepatitis B virus (HBV) expression and replication. METHODS The levels of miR-29a and SMARCE1 in HBV-infected HepG2.2.15 cells were measured by quantitative real-time PCR and western blot analysis. HBV DNA replication was measured by quantitative PCR and Southern blot analysis. The relative levels of hepat...

متن کامل

TGF-β Regulated miR-29a Promotes Angiogenesis through Targeting PTEN in Endothelium

The transforming growth factor-β (TGF-β) pathway plays important role in physiological and pathological angiogenesis. MicroRNAs (miRNAs) are a class of 18-25 nucleotides small noncoding RNAs that function by regulating gene expression. Numbers of miRNAs have been found to be regulated by TGF-β pathway. However, the role of endothelial miRNAs in the TGF-β-mediated control of angiogenesis is stil...

متن کامل

Hepatitis B Virus Induces Cell Proliferation via HBx-Induced microRNA-21 in Hepatocellular Carcinoma by Targeting Programmed Cell Death Protein4 (PDCD4) and Phosphatase and Tensin Homologue (PTEN)

Hepatitis B viral infection-induced hepatocellular carcinoma is one of the major problems in the developing countries. One of the HBV proteins, HBx, modulates the host cell machinery via several mechanisms. In this study we hypothesized that HBV enhances cell proliferation via HBx-induced microRNA-21 in hepatocellular carcinoma. HBx gene was over-expressed, and miRNA-21 expression and cell prol...

متن کامل

Expression of S and pre s2 Hepatitis B Surface Antigens in Mammalian Cos-7 Cell Line

Hepatitis B virus (HBV) is a serious global health problem. The development of a safe and effective vaccinewould help infection prevention. Previous hepatitis B vaccine production involved the isolation of the noninfectious particle from chronic HBV carriers. DNA recombinant technology has been used for vaccineproduction without having been contaminated with blood-born infectious ag...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 6  شماره 

صفحات  -

تاریخ انتشار 2011