title: miR-222 attenuates cisplatin-induced cell death by targeting the PPP2R2A/Akt/mTOR Axis in bladder cancer cells.
abstract: Increased miR-222 levels are associated with a poor prognosis in patients with bladder cancer. However, the role of miR-222 remains unclear. In the present study, we found that miR-222 enhanced the proliferation of both the T24 and the 5637 bladder cancer cell lines. Overexpression of miR-222 attenuated cisplatin-induced cell death in bladder cancer cells. miR-222 activated the Akt/mTOR pathway and inhibited cisplatin-induced autophagy in bladder cancer cells by directly targeting protein phosphatase 2A subunit B (PPP2R2A). Blocking the activation of Akt with LY294002 or mTOR with rapamycin significantly prevented miR-222-induced proliferation and restored the sensitivity of bladder cancer cells to cisplatin. These findings demonstrate that miR-222 modulates the PPP2R2A/Akt/mTOR axis and thus plays a critical role in regulating proliferation and chemotherapeutic drug resistance. Therefore, miR-222 may be a novel therapeutic target for bladder cancer.
authors.affiliation: The State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Zeng
authors.affiliation: The State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: Zheng-Mao
authors.initials: ZM
authors.lastname: Hu
authors.affiliation: The Clinical Laboratory of No.261 Hospital of the People's Liberation Army, Beijing, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
mesh_terms: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D001665:Binding Sites; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D054648:Protein Phosphatase 2 / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D001749:Urinary Bladder Neoplasms
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; D002945:Cisplatin; D035683:MicroRNAs; D054648:Protein Phosphatase 2; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C525710:MIR222, human; C512974:PPP2R2A protein, human; C546842:MTOR protein, human
keywords: bladder cancer; cisplatin; microRNA-222