title: The tumor-suppressive microRNA-135b targets c-myc in osteoscarcoma.
abstract: Osteosarcoma is the most common primary tumor of the bone. It leads to many deaths because of its rapid proliferation and metastasis. Recent studies have shown that microRNAs are important gene regulators that are involved in various cancer-related processes. In this study, we found that miR-135b was down-regulated in both osteoscarcoma patient tumor tissues and osteoscarcoma cell lines in comparison to paired adjacent non-tumor bone tissue. We observed that a lower level of miR-135b was associated with metastasis. The ectopic expression of miR-135b markedly suppressed osteoscarcoma cell proliferation, migration, and invasion. Conversely, the inhibition of miR-135b expression dramatically accelerated cell proliferation, migration, and invasion. The forced expression of miR-135b in osteosarcoma cells resulted in a significant reduction in the protein level of c-Myc and repressed the activity of a luciferase reporter that contained the 3'-untranslated region of the c-Myc mRNA. These effects were abolished by the mutation of the predicted miR-135b-binding site, which indicates that c-Myc may be a miR-135b target gene. Moreover, the ectopic expression of c-Myc partially reversed the inhibition of cell proliferation and invasion that was caused by miR-135b. These data therefore suggest that miR-135b may function as a tumor suppressor to regulate osteosarcoma cell proliferation and invasion through a mechanism that targets the c-Myc oncogene. These findings indicate that miR-135b may play a role in the pathogenesis of osteosarcoma.
authors.affiliation: Department of Orthopedic Surgery, Peking University Shougang Hospital, Beijing, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Orthopedic Surgery, Peking University Shougang Hospital, Beijing, China.
authors.forename: Guangwu
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, Peking University Shougang Hospital, Beijing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, Peking University Shougang Hospital, Beijing, China.
authors.forename: Jiabang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Orthopedic Surgery, Peking University Shougang Hospital, Beijing, China.
authors.forename: Pengfeng
authors.initials: P
authors.lastname: Lv
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D001665:Binding Sites; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002648:Child; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference
chemical_list: C544965:MIRN135 microRNA, human; C489427:MYC protein, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc