title: Receptor for activated protein kinase C: requirement for efficient microRNA function and reduced expression in hepatocellular carcinoma.
abstract: MicroRNAs (miRNAs) are important regulators of gene expression that control physiological and pathological processes. A global reduction in miRNA abundance and function is a general trait of human cancers, playing a causal role in the transformed phenotype. Here, we sought to newly identify genes involved in the regulation of miRNA function by performing a genetic screen using reporter constructs that measure miRNA function and retrovirus-based random gene disruption. Of the six genes identified, RACK1, which encodes "receptor for activated protein kinase C" (RACK1), was confirmed to be necessary for full miRNA function. RACK1 binds to KH-type splicing regulatory protein (KSRP), a member of the Dicer complex, and is required for the recruitment of mature miRNAs to the RNA-induced silencing complex (RISC). In addition, RACK1 expression was frequently found to be reduced in hepatocellular carcinoma. These findings suggest the involvement of RACK1 in miRNA function and indicate that reduced miRNA function, due to decreased expression of RACK1, may have pathologically relevant roles in liver cancers.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. otsukamo-tky@umin.ac.jp
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Otsuka
authors.forename: Akemi
authors.initials: A
authors.lastname: Takata
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kojima
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kishikawa
authors.forename: Chikako
authors.initials: C
authors.lastname: Shibata
authors.forename: Mutsuhiro
authors.initials: M
authors.lastname: Takekawa
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Yoshida
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Koike
mesh_terms: D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; C105789:KHSRP protein, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; C419368:RACK1 protein, human; D016601:RNA-Binding Proteins; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D019204:GTP-Binding Proteins