RT Journal Article
SR Electronic
T1 MiR-144 Inhibits Tumor Growth and Metastasis in Osteosarcoma via Dual-suppressing RhoA/ROCK1 Signaling Pathway
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 451
OP 461
DO 10.1124/mol.118.114207
VO 95
IS 4
A1 Jin Long Liu
A1 Jing Li
A1 Jia Jia Xu
A1 Fei Xiao
A1 Peng Lei Cui
A1 Zhi Guang Qiao
A1 Xiao Dong Chen
A1 Wei Dong Tao
A1 Xiao Ling Zhang
YR 2019
UL http://molpharm.aspetjournals.org/content/95/4/451.abstract
AB 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 miR-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 miR-144–transfected SAOS2 and U2-OS cells. Taken together, this study demonstrates that miR-144 inhibited tumor growth and metastasis in OS via dual-suppressing of RhoA and ROCK1, which could be a new therapeutic approach for the treatment of OS.