title: MiR-193a-3p and miR-193a-5p suppress the metastasis of human osteosarcoma cells by down-regulating Rab27B and SRR, respectively.
abstract: MicroRNAs have been identified as key players in the development and progression of osteosarcoma, which is the most common primary malignancy of bone. Sequencing-based miR-omic and quantitative real-time PCR analyses suggested that the expression of miR-193a-3p and miR-193a-5p was decreased by DNA methylation at their promoter region in a highly metastatic osteosarcoma cell line (MG63.2) relative to their expression in the less metastatic MG63 cell line. Further wound-healing and invasion assays demonstrated that both miR-193a-3p and miR-193a-5p suppressed osteosarcoma cell migration and invasion. Moreover, introducing miR-193a-3p and miR-193a-5p mimics into MG63.2 cells or antagomiRs into MG63 cells confirmed their critical roles in osteosarcoma metastasis. Additionally, bioinformatics prediction along with biochemical assay results clearly suggested that the secretory small GTPase Rab27B and serine racemase (SRR) were direct targets of miR-193a-3p and miR-193a-5p, respectively. These two targets are indeed involved in the miR-193a-3p- and miR-193a-5p-induced suppression of osteosarcoma cell migration and invasion. MiR-193a-3p and miR-193a-5p play important roles in osteosarcoma metastasis through down-regulation of the Rab27B and SRR genes and therefore may serve as useful biomarkers for the diagnosis of osteosarcoma and as potential candidates for the treatment of metastatic osteosarcoma.
authors.affiliation: Cancer Epigenetics Program, Anhui Cancer Hospital, Hefei, 230031, Anhui, China.
authors.forename: Youguang
authors.initials: Y
authors.lastname: Pu
authors.affiliation: Cancer Epigenetics Program, Anhui Cancer Hospital, Hefei, 230031, Anhui, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Orthopedic Surgery, Anhui Cancer Hospital, Hefei, 230031, Anhui, China.
authors.forename: Xianghui
authors.initials: X
authors.lastname: Meng
authors.affiliation: Xinxiang Medical University, Xinxiang, 453000, Henan, China.
authors.forename: Yinpeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Cancer Epigenetics Program, Anhui Cancer Hospital, Hefei, 230031, Anhui, China. shanbaocai651116@163.com.|Department of Orthopedic Surgery, Anhui Cancer Hospital, Hefei, 230031, Anhui, China. shanbaocai651116@163.com.
authors.forename: Shanbao
authors.initials: S
authors.lastname: Cai
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D019998:Racemases and Epimerases / Q000096:biosynthesis* / Q000235:genetics; D020691:rab GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D000099300:Serine Racemase
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D019998:Racemases and Epimerases; D020691:rab GTP-Binding Proteins; D000099300:Serine Racemase; C546818:MIRN193 microRNA, human; C512960:Rab27B protein, human
keywords: Metastasis; MiR-193a-3p and miR-193a-5p; Osteosarcoma; Rab27B; SRR