Oncotarget

Research Papers:

microRNA-135b expression silences Ppm1e to provoke AMPK activation and inhibit osteoblastoma cell proliferation

Zheng-Wei Li, Yun-Rong Zhu, Xiao-Zhong Zhou, Bao-Biao Zhuo and Xiao-Dong Wang _

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Oncotarget. 2017; 8:26424-26433. https://doi.org/10.18632/oncotarget.15477

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Abstract

Zheng-Wei Li1,*, Yun-Rong Zhu2,*, Xiao-Zhong Zhou3,4,*, Bao-Biao Zhuo1, Xiao-Dong Wang1

1The Center of Diagnosis and Treatment for Children’s Bone Diseases, The Children’s Hospital Affiliated to Soochow University, Suzhou, China

2Department of Orthopedics, The Affiliated Jiangyin Hospital of Medical College of Southeast University, Jiangyin City, China

3Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, China

4Department of Orthopedics, The First People’s Hospital of SuQian, SuQian, China

*Co-first authors

Correspondence to:

Xiao-Dong Wang, email: xiaodongwangsz@163.com

Keywords: microRNA-135b, Ppm1e, AMPK, osteoblastoma, cell proliferation

Received: January 20, 2017     Accepted: February 08, 2017     Published: February 18, 2017

ABSTRACT

Forced-activation of AMP-activated protein kinase (AMPK) can possibly inhibit osteoblastoma cells. Here, we aim to provoke AMPK activation via microRNA silencing its phosphatase Ppm1e (protein phosphatase Mg2+/Mn2+-dependent 1e). We showed that microRNA-135b-5p (“miR-135b-5p”), the anti-Ppm1e microRNA, was significantly downregulated in human osteoblastoma tissues. It was correlated with Ppm1e upregulation and AMPKα1 de-phosphorylation. Forced-expression of miR-135b-5p in human osteoblastoma cells (MG-63 and U2OS lines) silenced Ppm1e, and induced a profound AMPKα1 phosphorylation (at Thr-172). Osteoblastoma cell proliferation was inhibited after miR-135b-5p expression. Intriguingly, Ppm1e shRNA knockdown similarly induced AMPKα1 phosphorylation, causing osteoblastoma cell proliferation. Reversely, AMPKα1 shRNA knockdown or dominant negative mutation almost abolished miR-135b-5p’s actions in osteoblastoma cells. Further in vivo studies demonstrated that U2OS tumor growth in mice was dramatically inhibited after expressing miR-135b-5p or Ppm1e shRNA. Together, our results suggest that miR-135b-induced Ppm1e silence induces AMPK activation to inhibit osteoblastoma cell proliferation.


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