title: miR-126 inhibits cell growth, invasion, and migration of osteosarcoma cells by downregulating ADAM-9.
abstract: Osteosarcoma (OS) has become one of the most common primary malignant tumors in the children and adolescents with a poor prognosis mainly due to high metastasis. A disintegrin and metalloprotease 9 (ADAM-9) plays a role in tumorigenesis, invasion, and metastasis in several tumors. miR-126 has been reported to be downregulated in OS tumor. However, the involvement of ADAM-9 in the pathology of OS and the relationship between miR-126 and ADAM-9 in OS cells remain unclear. In this study, using quantitative reverse-transcribed PCR (qRT-PCR) analysis on 37 pairs of OS tumors and matched adjacent normal bone tissues, we found that ADAM-9 is significantly upregulated, while miR-126 is downregulated in human OS tumors. Association analysis revealed that upregulation of ADAM-9 and downregulation of miR-126 are significantly involved in advanced clinical stage development and distant metastasis. Luciferase reporter assay revealed that miR-126 could directly target ADAM-9 3' untranslated region (UTR) and inhibit its expression in U2OS and MG-63 cells. Functional experiments revealed that downregulating ADAM-9 by miR-126 inhibited cellular growth, invasion, and migration in U2OS and MG-63 cells. In rescue experiments, restored ADAM-9 expression attenuated miR-126-mediated suppression, while knockdown of ADAM-9 by small interfering RNA (siRNA) represented similar results with miR-126-mediated tumor suppression in U2OS cells. Taken together, our data indicated that miR-126 inhibits cell growth, invasion, and migration of OS cells by downregulating ADAM-9.
authors.affiliation: Department of Orthopedics, The Second Xiangya Hospital, Central South University, No. 139 Middle Renmin Road, Changsha, 410011, China, jiangliangdong@sina.com.
authors.forename: Liangdong
authors.initials: L
authors.lastname: Jiang
authors.forename: Aiyong
authors.initials: A
authors.lastname: He
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Cheng
authors.initials: C
authors.lastname: Tao
mesh_terms: D051722:ADAM Proteins / Q000737:chemistry / Q000235:genetics*; D000328:Adult; D000368:Aged; D001483:Base Sequence; D001665:Binding Sites; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology*; D034622:RNA Interference
chemical_list: C527111:MIRN126 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D051722:ADAM Proteins; C098339:ADAM9 protein, human