Knockdown of RhoQ, a member of Rho GTPase, accelerates TGF-β-induced EMT in human lung adenocarcinoma

Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide, and the most common subtype of lung cancer is adenocarcinoma. RhoQ is a Rho family GTPase with primary sequence and structural similarities to Cdc42 and RhoJ. RhoQ is involved in neurite outgrowth via membrane trafficking and is essential for insulin-stimulated glucose uptake in mature adipocytes. However, the function of RhoQ in lung adenocarcinoma (LUAD) remains unclear. In this study, RhoQ siRNAs were introduced into A549 and PC-9 cells. Expression level of EMT-related genes and invasion ability were investigated using Western blot and transwell assay. To examine the relationship between RhoQ expression and prognosis of LUAD, Kaplan–Meier plotter was used. We discovered that suppressing RhoQ expression promoted TGF-β-mediated EMT and invasion in LUAD cell lines. Furthermore, RhoQ knockdown increased Smad3 phosphorylation and Snail expression, indicating that RhoQ was involved in TGF/Smad signaling during the EMT process. Moreover, Kaplan–Meier plotter analysis revealed that low RhoQ levels were associated with poor overall survival in patients with LUAD. In conclusion, these findings shed light on RhoQ's role as a negative regulator of TGF-β-mediated EMT in LUAD.

Keywords

• EMT
• RhoQ
• Lung adenocarcinoma
• TGF-β