miR‐222 attenuates cisplatin‐induced cell death by targeting the PPP2R2A/Akt/mTOR Axis in bladder cancer cells

• Published in: Journal of cellular and molecular medicine Vol. 20; no. 3; pp. 559 - 567
• Main Authors: Zeng, Li‐Ping, Hu, Zheng‐Mao, Li, Kai, Xia, Kun
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 01.03.2016
• Subjects: 3' Untranslated Regions; Antineoplastic Agents - pharmacology; Base Sequence; Binding Sites; bladder cancer; Cell Death - drug effects; Cell Line, Tumor; Cell Proliferation; cisplatin; Cisplatin - pharmacology; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs - physiology; microRNA‐222; Original; Protein Phosphatase 2 - genetics; Protein Phosphatase 2 - metabolism; Proto-Oncogene Proteins c-akt - metabolism; RNA Interference; Signal Transduction; TOR Serine-Threonine Kinases - metabolism; Urinary Bladder Neoplasms; cisplatin; bladder cancer; microRNA-222
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.12760

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.