MicroRNA-375 functions as a tumor suppressor in osteosarcoma by targeting PIK3CA.

Osteosarcoma has become one of the most common primary malignant bone tumors in childhood and adult. Numerous studies have demonstrated that aberrant microRNA (miRNA) expression is involved in human disease including cancer. To date, the potential miRNAs regulating osteosarcoma growth and progression are not fully identified yet. Herein, we showed that miR-375 was frequently downregulated in osteosarcoma tissue and cell lines compared to normal human colon tissues. Overexpression of miR-375 resulted in decreased expression of PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) at both mRNA and protein levels. We found that miR-375 overexpression markedly suppressed cell proliferation in vitro. And inhibition of miR-375 promotes osteosarcoma growth. Mechanistic studies showed that PIK3CA was a potential target of miR-375 and it mediated reduction of PIK3CA resulted in suppression of PI3K/Akt pathway. Taken together, our results demonstrate that miR-375 functions as a growth-suppressive miRNA and plays an important role in inhibiting the tumorigenesis through targeting PIK3CA in osteosarcoma.