miR-141 modulates osteoblastic cell proliferation by regulating the target gene of lncRNA H19 and lncRNA H19-derived miR-675.

Abstract

Increasing evidence has reported the significant roles of lncRNA or miRNAs in the biology of various diseases. This study was aimed to elucidate the potential roles of miR-141 and lncRNA H19 and H19-derived miR-675 in regulating osteoblasts proliferation and apoptosis and to explore its potential mechanism. miR-141 mimic or miR-141 inhibitor or siRNA-H19 or miR-675 inhibitor was transfected into human hFOB1.19 cells. The effects or miR-141 expression on H19 or miR-675 expression, on osteoblasts proliferation and apoptosis were analyzed. Moreover, effects of H19 and miR-675 expression on cell proliferation were also analyzed. The results showed that miR-141 was down-regulated in both hFOB1.19 cells and osteosarcoma tissues. The overexpressed miR-141 suppressed H19 and miR-675 expression in hFOB1.19 cells. Besides, miR-141 suppression significantly increased cell viability but this effect was blocked by silencing H19 or miR-675 inhibitor, which is similar to the effects on VEGF and IGF2 expression. Furthermore, miR-141 overexpression induced osteoblasts apoptosis, but decreased the levels of caspase-3 and the Bcl-2/Bax ratio. Taken together, our study revealed that tumor-suppressor miR-141 overexpression suppressed osteoblasts proliferation but induced apoptosis through down-regulating H19 or miR-675 in osteosarcoma. This study may provide theoretical basis for illustrating the interaction between lncRNA and miRNAs in osteosarcoma and for the therapeutic target of miR-141 in osteosarcoma treatment.