Tumor-Suppressing Effects of miR451 in Human Osteosarcoma

Abstract

Osteosarcoma is the 3rd most common human cancer in childhood and young adults, and is the leading cause of mortality. Recent studies suggest that miRNAs could regulate the growth and progression of osteosarcoma, indicating some novel targets for therapy. In our study, we demonstrated that miR-451 was down-regulated in human osteosarcoma U2OS, SAOS, and MG63 cells lines as well as in tumor tissue surgically resected compared with the normal tissues. Overexpression of miR-451 inhibited cell proliferation and resulted in cell apoptosis in osteosarcoma cells. G1 cell cycle arrest was also induced by miR-451. Repressed by miR-451, PGE2 and CCND1 reversed the inhibitory effects of miR-451 on proliferation. In conclusion, miR-451 played a tumor-suppressing role through modulating the expression of PGE2 and CCND1, suggesting a novel target for the diagnosis and treatment of osteosarcoma.

miR-574-3p acts as a tumor promoter in osteosarcoma by targeting SMAD4 signaling pathway

“…Surgical specimens from 10 osteosarcoma and matched normal control tissues were obtained postoperatively in May 2010 from the Department of Orthopedics of Jinling Hospital, Nanjing University, School of Medicine (Nanjing, China) (3,5,10). All patients provided signed informed consent for their tissues to be used for scientific research.…”

“…The histological features of the specimens were evaluated by senior pathologists according to the World Health Organization classification criteria (11)(12)(13). Tissues were obtained prior to chemotherapy and radiotherapy, and were immediately frozen and stored at -80˚C prior to reverse-transcription quantitative polymerase chain reaction (RT-qPCR) assay (3,5,10).…”

“…Human osteosarcoma U2OS, SAOS and MG63 cell lines, and the normal human osteoblast cell line were obtained from Jinling Hospital Affiliated to Nanjing University (Nanjing, China), and maintained in Dulbecco's Modified Eagle's medium supplemented with 10% fetal bovine serum (GE Healthcare Bio-Sciences-Pittsburgh, PA, USA) (10). U2OS and MG63 cells were seeded in 24-well plates at a density of 6x10 4 (3). The proteins were transferred onto nitrocellulose membranes (GE Healthcare Life Sciences, Chalfont, UK), blocked with 5% milk and incubated overnight at 4˚C with the primary antibody anti-SMAD4 (1:1,500; cat.…”

“…Human osteosarcoma is the most common primary bone malignancy sarcoma found primarily in children and young people (1)(2)(3). The patients with osteosarcoma exhibit severe clinical manifestations, significantly diminished mobility and a reduced life expectancy (4,5).…”

“…The critical functions of numerous miRNAs in cancer biology have been illustrated, including the regulation of various cellular processes, such as proliferation and apoptosis (3,5,9,10). The abnormality of miR-574-3p was observed in patients with non-small cell lung cancer and prostate cancer, and it was found that this miRNA regulated colorectal cancer growth and plays important roles in bladder cancer cell lines (11)(12)(13).…”