AMPKα phosphatase Ppm1E upregulation in human gastric cancer is required for cell proliferation
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Min-Bin Chen1,*, Yuan-Yuan Liu1,*, Li-Bo Cheng2,*, Jian-Wei Lu3, Ping Zeng1, Pei-Hua Lu4
1Department of Radiotherapy and Oncology, Kunshan First People’s Hospital Affiliated to Jiangsu University, Kunshan, China
2Department of Ophthalmology, Wuxi Second Hospital, Nanjing Medical University, Wu'xi, China
3Department of Oncology, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing, China
4Department of Radiotherapy and Oncology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China
*These authors contributed equally to this work and co-first authors
Pei-Hua Lu, email: firstname.lastname@example.org
Keywords: gastric cancer, AMPKα, Ppm1E, mTOR, miR-135b-5p
Received: January 25, 2017 Accepted: February 15, 2017 Published: March 11, 2017
Activation of AMP-activated protein kinase (AMPK) is a valuable anti-cancer strategy. In the current study, we tested expression and potential function of Ca2+/calmodulin-dependent protein kinase phosphatase (Ppm1E), an AMPKα phosphatase, in human gastric cancers. Ppm1E expression was elevated in human gastric cancer tissues (vs. normal tissues), which was correlated with AMPK (p-AMPKα, Thr-172) dephosphorylation and mTOR complex 1 (mTORC1) activation. Ppm1E upregulation, AMPK inhibition and mTORC1 activation were also observed in human gastric cancer cell lines (AGS, HGC-27, and SNU601). Intriguingly, Ppm1E knockdown by shRNA induced AMPK activation, mTORC1 inactivation, and proliferation inhibition in AGS cells. On the other hand, forced over-expression of Ppm1E induced further AMPK inhibition and mTORC1 activation to enhance AGS cell proliferation. Remarkably, microRNA-135b-5p (“miR-135b-5p”), an anti-Ppm1E microRNA, was downregulated in both human gastric cancer tissues and cells. Reversely, miR-135b-5p exogenous expression caused Ppm1E depletion, AMPK activation, and AGC cell proliferation inhibition. Together, Ppm1E upregulation in human gastric cancer is important for cell proliferation, possible via regulating AMPK-mTOR signaling.
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