title: MiR-223 modulates hepatocellular carcinoma cell proliferation through promoting apoptosis via the Rab1-mediated mTOR activation.
abstract: Hepatocellular carcinoma (HCC) is a common digestive malignancy. MiR-223, a well-identified miRNA, exhibits diverse properties in different cancers. In this study, we demonstrated that miR-223 could suppress cell growth and promote apoptosis in HepG2 and Bel-7402 HCC cell lines. We screened and identified a novel miR-223 target, Ras-related protein Rab-1(Rab1). Upregulation of miR-223 would specifically and markedly down-regulate Rab1 expression. In addition, miR-223-overexpressing subclones showed significant cell growth inhibition by increasing cell apoptosis in HepG2 and Bel-7402 cells. To identify the mechanisms, we firstly investigated the mTOR pathway and found that pmTOR, p70S6K and Bcl-2 were dramatically down-regulated after miR-223 transfection, while no changes in the level of Bax was visualized. Furthermore, our data showed that the anti-tumor effects arising from miR-223 transfection in HCC cells may be due to the deactivation of mTOR pathway caused by the suppression of Rab1 expression when miR-223 is overexpressed. In summary, our results indicate that miR-223 functions as a tumor suppressor and plays a critical role in inhibiting the tumorigenesis and promoting the apoptosis of HCC through the mTOR signaling pathway in vitro. By targeting Rab1, miR-223 efficiently mediates the mTOR pathway. Given these, miR-223 may be a potential therapeutic target for treating HCC.
authors.affiliation: Comprehensive Liver Cancer Center, The 302 Hospital, Beijing, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of General Surgery, The 302 Hospital, Beijing, China.
authors.forename: Ruizhao
authors.initials: R
authors.lastname: Qi
authors.affiliation: Department of Pathology, The 302 Hospital, Beijing, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of General Surgery, The 302 Hospital, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Comprehensive Liver Cancer Center, The 302 Hospital, Beijing, China.
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Comprehensive Liver Cancer Center, The 302 Hospital, Beijing, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Comprehensive Liver Cancer Center, The 302 Hospital, Beijing, China.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Bai
authors.affiliation: Comprehensive Liver Cancer Center, The 302 Hospital, Beijing, China.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Chang
authors.affiliation: Department of Nursing, The 302 Hospital, Beijing, China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Hao
authors.affiliation: Comprehensive Liver Cancer Center, The 302 Hospital, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Comprehensive Liver Cancer Center, The 302 Hospital, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Lou
authors.affiliation: Department of General Surgery, The 302 Hospital, Beijing, China. Electronic address: LZW302@126.com.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Li
authors.affiliation: Comprehensive Liver Cancer Center, The 302 Hospital, Beijing, China. Electronic address: luyy302@163.com.
authors.forename: Yinying
authors.initials: Y
authors.lastname: Lu
mesh_terms: D017209:Apoptosis; D063646:Carcinogenesis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D020761:rab1 GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D058570:TOR Serine-Threonine Kinases; D020761:rab1 GTP-Binding Proteins; C525067:MIR223, human; C546842:MTOR protein, human
keywords: Apoptosis; Hepatocellular carcinoma; Rab1; mTOR; miR-223