miR-122 regulates tumorigenesis in hepatocellular carcinoma by targeting AKT3.
MicroRNAs (miRNAs) have been implicated in the orchestration of diverse cellular processes including differentiation, proliferation, and apoptosis and are believed to play pivotal roles as oncogenes and tumor suppressors. miR-122, a liver specific miRNA, is significantly down-regulated in most hepatocellular carcinomas (HCCs) but its role in tumorigenesis remains poorly understood. Here we identify AKT3 as a novel and direct target of miR-122. Restoration of miR-122 expression in HCC cell lines decreases AKT3 levels, inhibits cell migration and proliferation, and induces apoptosis. These anti-tumor phenotypes can be rescued by reconstitution of AKT3 expression indicating the essential role of AKT3 in miR-122 mediated HCC transformation. In vivo, restoration of miR-122 completely inhibited xenograft growth of HCC tumor in mice. Our data strongly suggest that miR-122 is a tumor suppressor that targets AKT3 to regulate tumorigenesis in HCCs and a potential therapeutic candidate for liver cancer.
Oncology Research, Pfizer Worldwide Research and Development, San Diego, California, United States of America.
Rounak
R
Nassirpour
Pramod P
PP
Mehta
Min-Jean
MJ
Yin
D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D020029:Base Pairing; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D023041:Xenograft Model Antitumor Assays
D020413:3' Untranslated Regions; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; C491754:AKT3 protein, human; D051057:Proto-Oncogene Proteins c-akt