Downregulation of miR-122 in the rodent and human hepatocellular carcinomas

J Cell Biochem. 2006 Oct 15;99(3):671-8. doi: 10.1002/jcb.20982.


MicroRNAs (miRs) are conserved small non-coding RNAs that negatively regulate gene expression. The miR profiles are markedly altered in cancers and some of them have a causal role in tumorigenesis. Here, we report changes in miR expression profile in hepatocellular carcinomas (HCCs) developed in male Fisher rats-fed folic acid, methionine, and choline-deficient (FMD) diet. Comparison of the miR profile by microarray analysis showed altered expression of some miRs in hepatomas compared to the livers from age-matched rats on the normal diet. While let-7a, miR-21, miR-23, miR-130, miR-190, and miR-17-92 family of genes was upregulated, miR-122, an abundant liver-specific miR, was downregulated in the tumors. The decrease in hepatic miR-122 was a tumor-specific event because it did not occur in the rats switched to the folate and methyl-adequate diet after 36 weeks on deficient diet, which did not lead to hepatocarcinogenesis. miR-122 was also silent in a transplanted rat hepatoma. Extrapolation of this study to human primary HCCs revealed that miR-122 expression was significantly (P = 0.013) reduced in 10 out of 20 tumors compared to the pair-matched control tissues. These findings suggest that the downregulation of miR-122 is associated with hepatocarcinogenesis and could be a potential biomarker for liver cancers.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Choline Deficiency
  • Diet
  • Folic Acid Deficiency
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Male
  • Methionine / deficiency
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Microarray Analysis
  • Rats
  • Rats, Inbred F344


  • MIRN190 microRNA, human
  • MicroRNAs
  • Methionine