title: MicroRNA-423 promotes cell growth and regulates G(1)/S transition by targeting p21Cip1/Waf1 in hepatocellular carcinoma.
abstract: MicroRNAs (miRNAs) are small non-coding RNA molecules that are often located in genomic breakpoint regions and can act as oncogenes or tumor suppressor genes in human cancer. Our previous study showed that microRNA-423 (miR-423), which localized to the frequently amplified region of chromosome 17q11, was upregulated in hepatocellular carcinoma (HCC). However, the potential functions and exact mechanistic roles of miR-423 in hepatic carcinogenesis remain unknown. Here, we demonstrated that miR-423 significantly promotes cell growth and cell cycle progression at the G(1)/S transition in HCC cells. In particular, we found that miR-423-3p contributes to these effects, whereas miR-423-5p does not. Further studies revealed that p21Cip1/Waf1 is a downstream target of miR-423 in HCC cells, as miR-423 bound directly to its 3' untranslated region and reduced both the messenger RNA and protein levels of p21Cip1/Waf1. Moreover, enforced expression of p21Cip1/Waf1 abrogated miR-423-induced effects on HCC cell proliferation and cell cycle progression. These findings indicate that miR-423 exerts growth-promoting effects in hepatic carcinogenesis through the suppression of tumor suppressor p21Cip1/Waf1 expression. The results of this study define miR-423 as a new oncogenic miRNA in HCC.
authors: Department of Hematology, Fujian Medical University Union Hospital, Fujian Institute of Hematology, No.29, Xin Quan Road, Fuzhou 350001, China.
authors: Jun
authors: J
authors: Lin
authors: Shenglin
authors: S
authors: Huang
authors: Shunquan
authors: S
authors: Wu
authors: Jie
authors: J
authors: Ding
authors: Yingjun
authors: Y
authors: Zhao
authors: Linhui
authors: L
authors: Liang
authors: Qi
authors: Q
authors: Tian
authors: Ruopeng
authors: R
authors: Zha
authors: Rong
authors: R
authors: Zhan
authors: Xianghuo
authors: X
authors: He
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D016193:G1 Phase / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008156:Luciferases / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D016196:S Phase / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D020413:3' Untranslated Regions; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C548900:MIRN423 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D008156:Luciferases