title: miR-92a promotes tumor growth of osteosarcoma by targeting PTEN/AKT signaling pathway.
abstract: MicroRNAs (miRNAs) play critical roles in human cancers including osteosarcoma (OS). miR-92a has been found to be a cancer-related miRNA in many cancer types and it is upregulated in OS cell lines. However, the expression and biological function of miR-92a in OS have not been investigated. In this study, we showed that miR-92a expression was increased in OS tissues, and its high expression was correlated with clinical stage, T classification and histological differentiation. Furthermore, patients with high expression of miR-92a had a significantly poorer survival rate. Functionally, miR-92a overexpression promoted the proliferation and cell cycle progression, and inhibited apoptosis in MG-63 cells. While inhibition of miR-92a showed contrary effects with reduced proliferation, cell cycle arrest at G1 phase and increased apoptosis in U2OS cells. Moreover, we confirmed that miR-92a inhibition reversed the tumor growth of OS cells in nude mice. Phosphatase and tensin homolog (PTEN), a well-known tumor suppressor, was confirmed to be the direct downstream target of miR-92a in OS. Notably, miR-92a consequently regulated the expression of the downstream targets of PTEN/AKT signaling pathway including p-Akt(Ser473), mTOR, p-p27(Thr157) and p-MDM2(Ser166). Furthermore, PTEN knockdown abrogated the functional effects of miR-92a silencing on the proliferation, apoptosis and cell cycle progression in OS cells. Thus, miR-92a that exerts an oncogenic role by targeting PTEN/AKT pathway in OS potentially acts as a biomarker and drug-target.
authors.affiliation: Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, P.R. China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Kongzu
authors.initials: K
authors.lastname: Hu
authors.affiliation: Department of Orthopaedic Surgery, Hangzhou First People's Hospital, Hangzhou, Zhejiang 310006, P.R. China.
authors.forename: Maoqiang
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, P.R. China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Orthopaedic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, P.R. China.
authors.forename: Zhanchun
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000473:pathology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D060787:Neoplasm Grading; D012516:Osteosarcoma / Q000235:genetics / Q000473:pathology*; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D015398:Signal Transduction; D016019:Survival Analysis
chemical_list: C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human