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

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机构： [1]The Center of Diagnosis and Treatment for Children's Bone Diseases, The Children’s Hospital Affiliated to Soochow University, Suzhou, China [2]Department of Orthopedics, The Affiliated Jiangyin Hospital of Medical College of Southeast University, Jiangyin City, China [3]Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, China [4]Department of Orthopedics, The First People’s Hospital of SuQian, SuQian, China

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关键词： microRNA-135b Ppm1e AMPK osteoblastoma cell proliferation

摘要：

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 AMPKa1 de-phosphorylation. Forced-expression of miR135b- 5p in human osteoblastoma cells (MG-63 and U2OS lines) silenced Ppm1e, and induced a profound AMPKa1 phosphorylation (at Thr-172). Osteoblastoma cell proliferation was inhibited after miR-135b-5p expression. Intriguingly, Ppm1e shRNA knockdown similarly induced AMPKa1 phosphorylation, causing osteoblastoma cell proliferation. Reversely, AMPKa1 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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出版当年[2016]版：

大类 | 1 区

医学

小类 | 2 区细胞生物学 2 区肿瘤学

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出版当年[2015]版：

Q1 CELL BIOLOGY Q1 ONCOLOGY

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影响因子： 0 最新[2023版] 0 最新五年平均 5.008 出版当年[2015版] 5.415 出版当年五年平均 6.359 出版前一年[2014版] 5.168 出版后一年[2016版]

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第一作者机构： [1]The Center of Diagnosis and Treatment for Children's Bone Diseases, The Children’s Hospital Affiliated to Soochow University, Suzhou, China

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通讯机构： [1]The Center of Diagnosis and Treatment for Children's Bone Diseases, The Children’s Hospital Affiliated to Soochow University, Suzhou, China

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