Downregulation of miR-122 in the rodent and human hepatocellular carcinomas.
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.
Kutay
Huban
H
Department of Molecular and Cellular Biochemistry, Ohio State University, Columbus, Ohio 43210, USA.
Bai
Shoumei
S
Datta
Jharna
J
Motiwala
Tasneem
T
Pogribny
Igor
I
Frankel
Wendy
W
Jacob
Samson T
ST
Ghoshal
Kalpana
K
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D002796:Choline Deficiency; D004032:Diet; D005494:Folic Acid Deficiency; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000172:deficiency; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D046228:Microarray Analysis; D051381:Rats; D011916:Rats, Inbred F344
C576613:MIRN190 microRNA, human; D035683:MicroRNAs; D008715:Methionine