A genetic variant in primary miR-378 is associated with risk and prognosis of hepatocellular carcinoma in a Chinese population

PLoS One. 2014 Apr 21;9(4):e93707. doi: 10.1371/journal.pone.0093707. eCollection 2014.

Abstract

Background: MiR-378 has been reported to be related to cell survival, tumor growth and angiogenesis and may participate in hepatocellular carcinoma (HCC) development and prognosis. Genetic variants in primary miR-378 (pri-miR-378) may impact miR-378 expression and contribute to HCC risk and survival. This study aimed to assess the associations between a genetic variant in primary miR-378 and HCC susceptibility and prognosis.

Methods: We conducted a case-control study to analyze the association of rs1076064 in pri-miR-378 with hepatocellular carcinoma risk in 1300 HCC patients with positive hepatitis B virus (HBV) and 1344 HBV carriers. Then, we evaluated the correlation between the polymorphism and hepatocellular carcinoma prognosis in 331 HCC patients at either intermediate or advanced stage without surgical treatment.

Results: The variant genotypes of rs1076064 were associated with a decreased HCC risk in HBV carriers [Adjusted odds ratio (OR) = 0.90, 95% confidence intervals (CI) = 0.81-1.00, P = 0.047]. Moreover, HCC patients with the variant genotypes were associated with a better survival [Adjusted hazard ratio (HR) = 0.70, 95% CIs = 0.59-0.83, P<0.0001 in an additive genetic model]. The reporter gene assay showed that the variant G allele of rs1076064 exerted higher promoter activity than the A allele.

Conclusions: These findings indicate that rs1076064 may be a biomarker for HCC susceptibility and prognosis through altering pri-miR-378 transcription.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alleles
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / virology
  • Cell Line, Tumor
  • Gene Frequency / genetics
  • Genetic Predisposition to Disease*
  • Hepatitis B / genetics
  • Hepatitis B / virology
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / virology
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Multivariate Analysis
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • Proportional Hazards Models
  • Risk Factors
  • Survival Analysis

Substances

  • MIRN378 microRNA, human
  • MicroRNAs

Grants and funding

This work was supported by the National Natural Science Foundation of China (81372606 and 81072344), Project supported by the National Key Basic Research Program Grant (2013CB911400), the project supported by the National Science Foundation for Distinguished Young Scholars of China (81225020), Foundation of Jiangsu Province for Distinguished Young Scholars (BK2012042), Foundation for the Program for New Century Excellent Talents in University (NCET-10-0178), the Fok Ying-Tong Education Foundation for Young Teachers in the Higher Education Institutions (122031), Young tip-top talents support program by the Organization Department of the CPC Central Committee, the Author of National Excellent Doctoral Dissertation (201081) , Jiangsu Province Clinical Science and Technology Projects (BL2012008) and the Priority Academic Program for the Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.