title: MicroRNA-133a, downregulated in osteosarcoma, suppresses proliferation and promotes apoptosis by targeting Bcl-xL and Mcl-1.
abstract: Deregulated microRNAs and their roles in cancer development have attracted much attention. Although miR-133a has been shown to be important in osteogenesis, its roles in osteosarcoma carcinogenesis and progression remain unknown. Hence, we focused on the expression and mechanisms of miR-133a in osteosarcoma development in this study. We found that miR-133a was downregulated in osteosarcoma cell lines and primary human osteosarcoma tissues, and its decrease was significantly correlated with tumor progression and prognosis of the patients. Functional studies revealed that restoration of miR-133a could reduce cell proliferation, promote cell apoptosis, and suppress tumorigenicity in osteosarcoma cell lines. Furthermore, bioinformatic prediction and experimental validation were applied to identify target genes of miR-133a, and the results revealed that the anti-tumor effect of miR-133a was probably due to targeting and repressing of Bcl-xL and Mcl-1 expression. Taken together, our data elucidate the roles of miR-133a in osteosarcoma pathogenesis and implicate its potential in cancer therapy.
authors.affiliation: Department of Orthopedics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Ji
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Weidong
authors.initials: W
authors.lastname: Xu
authors.forename: Yifan
authors.initials: Y
authors.lastname: Kang
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
authors.forename: Zimin
authors.initials: Z
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Cheng
authors.forename: Dake
authors.initials: D
authors.lastname: Tong
authors.forename: Cheng
authors.initials: C
authors.lastname: Li
authors.forename: Hao
authors.initials: H
authors.lastname: Tang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism*; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology*; D011379:Prognosis; D051020:bcl-X Protein / Q000378:metabolism*
chemical_list: C579095:MCL1 protein, human; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D051020:bcl-X Protein
keywords: Apoptosis; Bcl-xL; Mcl-1; MicroRNA; Osteosarcoma; miR-133a