title: miR-34a is downregulated in human osteosarcoma stem-like cells and promotes invasion, tumorigenic ability and self-renewal capacity.
abstract: MicroRNA-34 (miR-34), in particular miR-34a, has a negative regulatory effect on osteosarcoma cell proliferation, migration and invasion. Notably, it is also a post‑transcriptional regulatory factor of (sex determining region Y)‑box 2 (Sox-2), which is required for osteosarcoma cell self‑renewal and tumorigenesis. As a direct regulator of Sox‑2, miR‑34a has been hypothesized to be greatly associated with the regulation of malignancies in osteosarcoma. To investigate the role of miR-34a in the malignancies of osteosarcoma, reverse transcription‑quantitative polymerase chain reaction was performed to detect the expression level of miR‑34a in osteospheres. The results revealed that the miR‑34a, b and c were suppressed in osteosarcoma stem‑like cells (OSCs) and osteospheres. The introduction of miR‑34a mimics and short hairpin (sh)RNA targeting Sox‑2 mRNA (shSox‑2) in human OSCs markedly reduced their transformation properties in vitro and their capacity to form tumors in soft agar. Furthermore, the epigenetic expression of miR‑34a and shSox‑2 inhibited the expression of the stem cell marker, stem cell antigen‑1 and led to the failure of osteosphere formation, respectively. The data of the present study indicated that the inhibitory role of miR‑34a on tumor growth and metastasis of osteosarcoma may function by reducing the maintenance of osteosphere self‑renewal capacity, elimination of tumorigenic ability and invasion of osteosarcoma in vitro. These findings may provide the basis for a novel therapeutic target of osteosarcomas based on inducing the expression of miR-34a.
authors.affiliation: Department of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.
authors.forename: Yonggen
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Department of Transfusion, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.
authors.forename: Yuanshuai
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.
authors.forename: Jiexiang
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Luo
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D000066673:Cell Self Renewal / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000473:pathology*; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D018874:Spheroids, Cellular / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D055748:SOXB1 Transcription Factors