MicroRNA 181a improves proliferation and invasion, suppresses apoptosis of osteosarcoma cell

Abstract

MicroRNA 181a (miR-181a) was found dysregulated in a variety of human cancers and significantly associated with clinical outcome of cancer patients. However, the direct role of miR-181a has not yet been characterized in osteosarcoma progression. This study was aimed at investigating the effects of miR-181a on osteosarcoma cell biological behavior. First, the expression of miR-181a in osteosarcoma cell lines (MG63, HOS, SaOS-2, and U2OS) and a human osteoblastic cell line (hFOB1.19) was detected by qRT-PCR. Results showed that miR-181a was overexpressed in osteosarcoma cell lines compared to human osteoblastic cell line (hFOB1.19). To investigate the effects of miR-181a on proliferation, apoptosis, and invasion of osteosarcoma cells, we generated human osteosarcoma MG63 cells in which miR-181a was either overexpressed or depleted. The MG63 cell viability, cycle, apoptosis, and invasive ability were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide staining, propidium iodide (PI) staining, Annexin V-FITC/PI double staining, and Transwell invasion experiment, respectively. The results showed that MG63 cell viability, proliferation, and invasive abilities were suppressed, and the apoptosis was enhanced in the group with underexpression of miR-181a. The viability, proliferation, and invasive abilities were improved, and the apoptosis was inhibited in the group with overexpression of miR-181a. The results from Western blotting indicated that miR-181a might be associated with the up-regulation of bcl-2 and matrix metalloproteinase 9 and the down-regulation of tissue inhibitor of metalloproteinases-3 and p21 in MG63 cells. Taken together, our results suggested that miR-181a might facilitate proliferation and invasion and suppress apoptosis of osteosarcoma cells, which might be a potential target for the treatment of osteosarcoma.

MiR-181a Targets PHLPP2 to Augment AKT Signaling and Regulate Proliferation and Apoptosis in Human Keloid Fibroblasts

“…In contrast, miR-181a is reported to promote G1/S transition and cell proliferation in pediatric acute myeloid leukemia by targeting ATM [18]. Jianwei and colleges demonstrated that miR-181a improves proliferation and invasion and suppresses apoptosis of osteosarcoma cells [19]. Data from the current study showed that miR-181a is increased in human keloid fibroblasts, although its functions and molecular mechanisms remain to be established.…”

CORR Insights®: MicroRNA Regulates Vascular Endothelial Growth Factor Expression in Chondrosarcoma Cells

“…Normal chondrocytes, chondrosarcoma, and osteosarcoma have been shown to express miRNA-181a [1,2,6,9]. The current study has made an important contribution in terms of how it demonstrates a pathogenic role for miR181a, particularly in terms of the upregulation of VEGF, and how it may respond to hypoxia in chondrosarcoma cells.…”

“…Previous studies [1,2,6,9] demonstrated that miRNA-181a is neither cell nor tumor specific. Normal chondrocytes, chondrosarcoma, and osteosarcoma have been shown to express miRNA-181a [1,2,6,9].…”

“…Still, the roles cannot be defined without more data. In order to obtain these data, we must ask questions like (1) what are the relationships between the miRNAs and other cytokines which upregulate the expression of the VEGF? (2) Can miRNA-181a regulate other angiogenesis growth factors?…”

“…Previous research [5] demonstrated the roles of miRNAs in tumor initiation, invasion, angiogenesis, apoptosis, and metastasis, among other areas. A number of articles [1][2][3][4][5][6][7][8][9] have investigated miRNAs in sarcomas. Yoshitaka and colleagues [9] evaluated the miRNA expressions in clinical samples from human conventional chondrosarcoma tissue, cell lines, and nontumorous articular chondrocytes.…”