Repression of RhoJ expression promotes TGF-β-mediated EMT in human non-small-cell lung cancer A549cells

Biochem Biophys Res Commun. 2021 Aug 20;566:94-100. doi: 10.1016/j.bbrc.2021.06.004. Epub 2021 Jun 10.

Abstract

Non-small-cell lung cancer (NSCLC) accounts for most cancer-related deaths because of its strong metastatic ability. It is important to understand NSCLC's molecular mechanisms of metastasis. RhoJ, a protein that belongs to the Rho family of small GTPases, regulates endothelial motility, angiogenesis, and adipogenesis. Recently, bioinformatics analysis showed that NSCLC patients with lower RhoJ expression had a worse survival outcome than those with high RhoJ expression. However, little is known about RhoJ's role in NSCLC. In the present study, we demonstrated that RhoJ knockdown accelerated TGF-βmediated epithelial-to-mesenchymal transition (EMT), an important cancer metastasis process, in A549 and PC-9 cells. Furthermore, using Matrigel-coated transwell chambers, we showed that RhoJ knockdown enhanced the invasion capacity of A549 cells that had undergone EMT. Also, reduced RhoJ expression increased Smad3 phosphorylation and Snail expression during the EMT process. Our results provide the first evidence of a potential novel role for RhoJ in the inhibition of EMT via modulation of the TGF-β-Smad signaling pathway, and shed new light on the mechanisms underlying EMT in NSCLC.

Keywords: EMT; Invasion capacity; Non-small-cell lung cancer; RhoJ; TGF-β.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Down-Regulation
  • Epithelial-Mesenchymal Transition*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Transforming Growth Factor beta / metabolism*
  • rho GTP-Binding Proteins / genetics*
  • rho GTP-Binding Proteins / metabolism

Substances

  • Transforming Growth Factor beta
  • RHOJ protein, human
  • rho GTP-Binding Proteins