MiR-144 Inhibits Tumor Growth and Metastasis in Osteosarcoma via Dual-suppressing RhoA/ROCK1 Signaling Pathway

摘要

Several microRNAs (miRNAs) have been found expressed differentially in osteosarcoma (OS), so they may function in the onset and progression of OS. In this study, we found that miR-144 significantly suppresses osteosarcoma cell proliferation, migration, and invasion ability in vitro and inhibited tumor growth and metastasis in vivo. Mechanically, we demonstrated that Ras homolog family member A (RhoA) and its pivotal downstream effector Rho-associated, coiled-coil-containing protein kinase 1 (ROCK1) were direct targets of miR-144. Moreover, the negative correlation between down-regulated nniR-144 and up-regulated ROCK1/RhoA was verified in both OS cell lines and clinical patients' specimens. Functionally, RhoA with or without ROCK1 co-overexpression resulted a rescue phenotype on miR-144 inhibited cell growth, migration, and invasion abilities whereas individual overexpression of ROCK1 had no statistical significance compared with controls in nniR-144-transfected SAOS2 and U2-OS cells. Taken together, this study demonstrates that miR-144 inhibited tumor growth and metastasis OS via dual-suppressing of RhoA and ROCK1, which could be a new therapeutic approach for the treatment of OS.