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	Li-Ping Zeng, Zheng-Mao Hu, Kai Li, Kun Xia
Journal	Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 20 Issue 3 Pg. 559-67 (Mar 2016) ISSN: 1582-4934 [Electronic] England
PMID	26800397 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	© 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
Chemical References	3' Untranslated Regions Antineoplastic Agents MIRN222 microRNA, human MicroRNAs PPP2R2A protein, human MTOR protein, human Proto-Oncogene Proteins c-akt TOR Serine-Threonine Kinases Protein Phosphatase 2 Cisplatin
Topics	3' Untranslated Regions Antineoplastic Agents (pharmacology) Base Sequence Binding Sites Cell Death (drug effects) Cell Line, Tumor Cell Proliferation Cisplatin (pharmacology) Drug Resistance, Neoplasm Drug Screening Assays, Antitumor Gene Expression Regulation, Neoplastic Humans MicroRNAs (physiology) Protein Phosphatase 2 (genetics, metabolism) Proto-Oncogene Proteins c-akt (metabolism) RNA Interference Signal Transduction TOR Serine-Threonine Kinases (metabolism) Urinary Bladder Neoplasms

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