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

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.

Liu JL ，Li J ，Xu JJ ，Xiao F ，Cui PL ，Qiao ZG ，Chen XD ，Tao WD ，Zhang XL ... -  《-》

Long noncoding RNA DANCR, working as a competitive endogenous RNA, promotes ROCK1-mediated proliferation and metastasis via decoying of miR-335-5p and miR-1972 in osteosarcoma.

Wang Y ，Zeng X ，Wang N ，Zhao W ，Zhang X ，Teng S ，Zhang Y ，Lu Z ... -  《Molecular Cancer》

MicroRNA-144 suppresses osteosarcoma growth and metastasis by targeting ROCK1 and ROCK2.

Wang W ，Zhou X ，Wei M 《Oncotarget》

MicroRNA-129-5p suppresses cell proliferation, migration and invasion via targeting ROCK1 in osteosarcoma.

Han C ，Wang W 《-》

Long non-coding RNA SNHG5 sponges miR-26a to promote the tumorigenesis of osteosarcoma by targeting ROCK1.

Osteosarcoma (OS) is one of the most common invasive malignancies of the bone. The long non-coding RNA (lncRNA) SNHG5 (small nucleolar RNA host gene 5) has been consistently shown to be involved in many cancers, although its precise function in osteosarcoma remains poorly understood. In this study, we investigated the role of SNHG5 in OS progression and the underlying mechanism. SNHG5 expression in 32 OS tissues and 4 OS cell lines was measured by quantitative real-time PCR (qRT-PCR). Migration, invasion, proliferation and cell cycle profiles were analyzed by established assays to determine the biological functions of SNHG5 and miR-26a in OS cells. The binding sites of miR-26a in SNHG5 and ROCK1 were predicted by the RNAhybrid 2.2 program. Luciferase reporter assay was then used to validate the direct targeting of SNHG5 with miR-26a and of Rho-associated coiled coil-containing protein kinase 1 (ROCK1) with miR-26a. The effect of SNHG5 on the ROCK signaling pathway was assessed by western blotting. Elevated expression of SNHG5 was correlated with poor clinical outcome and prognosis in OS patients. SNHG5 functioned as a sponge for miR-26a and promoted proliferation, invasion and migration, and accelerated G1 to S phase transition in OS cells. SNHG5 functioned as a competing endogenous RNA (ceRNA) for miR-26a and activated the ROCK signaling pathway through the miR-26a-ROCK1 axis. SNHG5 acts as an oncogene in OS via the SNHG5-miR-26a-ROCK1 axis and is therefore a potential novel therapeutic target for OS treatment.

Wang Z ，Wang Z ，Liu J ，Yang H ... -  《-》