PT  - JOURNAL ARTICLE
AU  - Jin Long Liu
AU  - Jing Li
AU  - Jia Jia Xu
AU  - Fei Xiao
AU  - Peng Lei Cui
AU  - Zhi Guang Qiao
AU  - Xiao Dong Chen
AU  - Wei Dong Tao
AU  - Xiao Ling Zhang
TI  - MiR-144 Inhibits Tumor Growth and Metastasis in Osteosarcoma via Dual-suppressing RhoA/ROCK1 Signaling Pathway
AID  - 10.1124/mol.118.114207
DP  - 2019 Apr 01
TA  - Molecular Pharmacology
PG  - 451--461
VI  - 95
IP  - 4
4099  - http://molpharm.aspetjournals.org/content/95/4/451.short
4100  - http://molpharm.aspetjournals.org/content/95/4/451.full
SO  - Mol Pharmacol2019 Apr 01; 95
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.