Regulation of the expression of the liver cancer susceptibility gene MICA by microRNAs.
Hepatocellular carcinoma (HCC) is a threat to public health worldwide. We previously identified the association of a single nucleotide polymorphism (SNP) at the promoter region of the MHC class I polypeptide-related sequence A (MICA) gene with the risk of hepatitis-virus-related HCC. Because this SNP affects MICA expression levels, regulating MICA expression levels may be important in the prevention of HCC. We herein show that the microRNA (miR) 25-93-106b cluster can modulate MICA levels in HCC cells. Overexpression of the miR 25-93-106b cluster significantly suppressed MICA expression. Conversely, silencing of this miR cluster enhanced MICA expression in cells that express substantial amounts of MICA. The changes in MICA expression levels by the miR25-93-106b cluster were biologically significant in an NKG2D-binding assay and an in vivo cell-killing model. These data suggest that the modulation of MICA expression levels by miRNAs may be a useful method to regulate HCCs during hepatitis viral infection.
1] Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan [2].
Takahiro
T
Kishikawa
Motoyuki
M
Otsuka
Takeshi
T
Yoshikawa
Motoko
M
Ohno
Akemi
A
Takata
Chikako
C
Shibata
Yuji
Y
Kondo
Masao
M
Akanuma
Haruhiko
H
Yoshida
Kazuhiko
K
Koike
D020413:3' Untranslated Regions; D000818:Animals; D020029:Base Pairing; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D020022:Genetic Predisposition to Disease; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D034622:RNA Interference
D020413:3' Untranslated Regions; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; D035683:MicroRNAs