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J Cell Mol Med. 2016 Mar;20(3):559-67. doi: 10.1111/jcmm.12760. Epub 2016 Jan 22.

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

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The State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
The Clinical Laboratory of No.261 Hospital of the People's Liberation Army, Beijing, China.


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.


bladder cancer; cisplatin; microRNA-222

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