title: The microRNA-29 plays a central role in osteosarcoma pathogenesis and progression.
abstract: Osteosarcoma is the most common type of bone cancer, with a peak incidence in the early childhood. The relationship between microRNAs (miRNAs) and cancer development attracted more and more attention over the last few years. Members of the miRNA-29 family, including miRNA-29a, miRNA-29b, and miRNA-29c were shown to participate in the development of rhabdomyosarcoma and hepatocarcinogenesis. Here, it has been demonstrated miRNA-29a and miRNA-29b expression levels to be downregulated in most of the osteosarcoma tissues (23 from 30). Besides, miRNA-29a displayed ability to induce apoptosis in both U2OS and SAOS-2 osteoblastic cells. While miRNA-29 members induced apoptosis through p53 gene activation, the effect of miRNA-29a on osteoblastic cells was independent on p53 expression level. Moreover, Bcl-2 and Mcl-1 were earlier demonstrated to be the direct targets of miRNA-29 in many types of cancer tissues and cancers. In both U2OS and SAOS-2 osteoblastic cell types, overexpression of miRNA-29a also downregulated Bcl-2 and Mcl-1, while silencing of miRNA-29a increased their expression. In addition, enhanced expression of miRNA-29a increased the expression of two tumor suppressor genes, E2F1 and E2F3. In summary, data obtained highlight the role of miRNA-29a in the regulation of osteoblastic cell apoptosis by silencing Bcl-2 and Mcl-1 and inducing E2F1 and E2F3 expression.
authors.affiliation: Department of Orthopedics, the No. 401 Hospital ofPLA, 22 Minjiang Road, Qingdao, Shandong, 266071, China.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: J-X
authors.initials: JX
authors.lastname: Qian
authors.forename: H-L
authors.initials: HL
authors.lastname: Yi
authors.forename: Z-D
authors.initials: ZD
authors.lastname: Yang
authors.forename: C-F
authors.initials: CF
authors.lastname: Wang
authors.forename: J-Y
authors.initials: JY
authors.lastname: Chen
authors.forename: X-Z
authors.initials: XZ
authors.lastname: Wei
authors.forename: Q
authors.initials: Q
authors.lastname: Fu
authors.forename: H
authors.initials: H
authors.lastname: Ma
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D015536:Down-Regulation; D050687:E2F1 Transcription Factor / Q000378:metabolism; D050699:E2F3 Transcription Factor / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D010006:Osteoblasts / Q000378:metabolism* / Q000473:pathology; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D019076:Transgenes / Q000235:genetics
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D050699:E2F3 Transcription Factor; C098319:E2F3 protein, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2