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

  1. Huban Kutay1,
  2. Shoumei Bai1,
  3. Jharna Datta1,
  4. Tasneem Motiwala1,
  5. Igor Pogribny5,
  6. Wendy Frankel2,
  7. Samson T. Jacob1,3,4,
  8. Kalpana Ghoshal1,*

Article first published online: 30 JUN 2006

DOI: 10.1002/jcb.20982

Issue

Journal of Cellular Biochemistry

Journal of Cellular Biochemistry

Volume 99, Issue 3, pages 671–678, 15 October 2006

Additional Information

How to Cite

Kutay, H., Bai, S., Datta, J., Motiwala, T., Pogribny, I., Frankel, W., Jacob, S. T. and Ghoshal, K. (2006), Downregulation of miR-122 in the rodent and human hepatocellular carcinomas. J. Cell. Biochem., 99: 671–678. doi: 10.1002/jcb.20982

Author Information

  1. 1

    Department of Molecular and Cellular Biochemistry, Ohio State University, Columbus, Ohio 43210

  2. 2

    Department of Pathology, Ohio State University, Columbus, Ohio 43210

  3. 3

    Internal Medicine, College of Medicine, Ohio State University, Columbus, Ohio 43210

  4. 4

    Comprehensive Cancer Center, Ohio State University, Columbus, Ohio 43210

  5. 5

    Division of Biochemical Toxicology, Food and Drug Administration, National Center for Toxicological Research, Jefferson, Arkansas 72079

*Department of Molecular and Cellular Biochemistry, Ohio State University, 319 Hamilton Hall, Columbus, OH 43210.

Publication History

  1. Issue published online: 25 SEP 2006
  2. Article first published online: 30 JUN 2006
  3. Manuscript Accepted: 11 APR 2006
  4. Manuscript Received: 7 APR 2006

Funded by

  • NIH. Grant Number: CA86978

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Keywords:

  • folate/methyl-deficient diet;
  • hepatocellular carcinoma;
  • microRNA;
  • miR-122;
  • miR-17-92;
  • miR-21

Abstract

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. J. Cell. Biochem. 99: 671–678, 2006. © 2006 Wiley-Liss, Inc.

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