title: Overexpression of miR-92a promotes the tumor growth of osteosarcoma by suppressing F-box and WD repeat-containing protein 7.
abstract: MicroRNAs (miRNAs) have been reported to be critical players in osteosarcoma (OS). Among numerous cancer-related miRNAs, the expression level of miR-92a and its potential role in OS has not been investigated. Here, We showed that overexpression of miR-92a was identified in OS specimens and cells compared to normal bone tissues. The high level of miR-92a was correlated with high T classification and advanced clinical stages of OS patients. Notably, miR-92a highly expressing OS patients showed a notably reduced survival rate. In vitro experiments showed that loss of miR-92a inhibited U2OS cell proliferation and cell-cycle progression while induced apoptosis. In turn, its restoration facilitated MG-63 cell growth and suppressed apoptosis. Experimental nude mice showed that miR-92a silencing prohibited the in vivo growth of OS cells. Furthermore, bioinformatics software predicted that F-box and WD repeat-containing protein 7 (FBXW7) was a direct target of miR-92a. We then observed the negative regulation of miR-92a on FBXW7 expression and the direct binding between them was further verified by dual-luciferase assays in OS cells. Forced expression of FBXW7 resulted in reduced proliferation, cell cycle arrest at G1 phase and increased apoptosis in miR-92a overexpressing MG-63 cells. In summary, this study demonstrates miR-92a probably functions as a driver of tumor progression by targeting FBXW7, and highlights the potential effects of miR-92a on prognosis and treatment of OS.
authors.affiliation: Department of Orthopedics, Huzhou Central Hospital, Huzhou, Zhejiang 313003, China.
authors.forename: Xuesheng
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Orthopedics, Huzhou Central Hospital, Huzhou, Zhejiang 313003, China.
authors.forename: Xiongfeng
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Huzhou Central Hospital, Huzhou, Zhejiang 313003, China.
authors.forename: Fengfeng
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Orthopedics, Huzhou Central Hospital, Huzhou, Zhejiang 313003, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Orthopedics, Huzhou Central Hospital, Huzhou, Zhejiang 313003, China.
authors.forename: Guorong
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Huzhou Central Hospital, Huzhou, Zhejiang 313003, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, China.
authors.forename: Huajun
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Huzhou Central Hospital, Huzhou, Zhejiang 313003, China. Electronic address: wwl_zzu@163.com.
authors.forename: Jianyou
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Orthopedics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China. Electronic address: chenchao_smu@163.com.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D044783:F-Box Proteins / Q000378:metabolism*; D000073979:F-Box-WD Repeat-Containing Protein 7; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D044767:Ubiquitin-Protein Ligases
keywords: Apoptosis; Cell cycle progression; FBXW7; Osteosarcoma; Proliferation; miR-92a