title: Antitumor function of microRNA-122 against hepatocellular carcinoma.
abstract: MicroRNA-122 (miR-122), a highly abundant and liver-specific miRNA, acts as a tumor suppressor against hepatocellular carcinoma (HCC). Decreased expression of miR-122 in HCC is frequently observed and is associated with poor differentiation, larger tumor size, metastasis and invasion, and poor prognosis. Mutant mice with knockout (KO) of the miR-122 locus developed steatohepatitis due to increased triglyceride (TG) synthesis and decreased TG secretion from hepatocytes, and eventually developed HCC. Exogenic miR-122 introduction into miR-122 KO mice inhibited the development of HCC. Target genes of miR-122, including cyclin G1, a disintegrin and metalloprotease (ADAM)10, serum response factor, insulin-like growth factor-1 receptor, ADAM17, transcription factor CUTL1, the embryonic isoform of pyruvate kinase (Pkm2), Wnt1, pituitary tumor-transforming gene 1 binding factor, Cut-like homeobox 1, and c-myc, are involved in hepatocarcinogenesis, epithelial mesenchymal transition, and angiogenesis. MiR-122 expression is regulated by liver-enriched transcription factors such as hepatocyte nuclear factor (HNF)1α, HNF3β, HNF4α, HNF6, and CCAAT/enhancer-binding protein (C/EBP)α. A positive feedback loop exists between C/EBPα and miR-122 and between HNF6 and miR-122, whereas a negative feedback loop exists between c-myc and miR-122. Since cotreatment of 5-Aza-Cd and histone deacetylase inhibitor restored miR-122 expression in HCC cells, epigenetic modulation of miR-122 expression is involved in the suppression of miR-122 in HCC. Several experiments suggest that increasing miR-122 levels in HCC with or without antitumor agents may be a promising strategy for HCC treatment.
authors: Department of Gastroenterology and Hepatology, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto 1-7-1, Nagasaki, 852-8501, Japan, kazuhiko@nagasaki-u.ac.jp.
authors: Kazuhiko
authors: K
authors: Nakao
authors: Hisamitsu
authors: H
authors: Miyaaki
authors: Tatsuki
authors: T
authors: Ichikawa
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000188:drug therapy / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015536:Down-Regulation; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics* / Q000627:therapeutic use
chemical_list: C531907:MIRN122 microRNA, human; D035683:MicroRNAs