ARID2 Suppresses Cell Proliferation, Migration, and Invasion of Colon Cancer by the TGF-β1/Smad Pathway

Abstract

Background: Colon cancer (CC) is associated with high morbidity and mortality rates. AT-rich interaction domain 2 (ARID2) is a tumor suppressor that is commonly mutated in various cancers. In this study, we aimed to explore whether ARID2 functions in CC and its underlying mechanisms. Methods: ARID2 expression was measured by quantitative real-time PCR (polymerase chain reaction) immunohistochemical assay, and western blotting. After CC cells were transfected with ARID2 overexpression vector and/or treated with SRI-011381 (transforming growth factor beta 1 (TGF-β1)/Smad (small mothers against decapentaplegic) pathway activator), the cells were divided into oe-negative control (NC), oe-ARID2 (the ARID2 overexpression vector), and oe-ARID2 + SRI-011381 groups, the biological functions, including cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), were analyzed using cell counting kit-8, colony formation analysis, Transwell assay, and western blotting, respectively. The TGF-β1/Smad pathway affected by ARID2 were measured by western blotting. Effects of ARID2 on tumor weight and volume were evaluated in a xenograft tumor model in the adenovirus (Ad)-NC and Ad-ARID2 groups. Results: ARID2 was downregulated at the mRNA and protein levels in CC tissues and cells. Aberrant ARID2 expression has diagnostic and prognostic value. ARID2 overexpression suppresses CC cell proliferation, invasion, migration, and EMT. ARID2 downregulated TGF-β1, p-Smad2, and p-Smad3 protein levels. Upregulation of TGF-β1 partly abrogated the effects of ARID2 on biological behavior. Moreover, ARID2 overexpression inhibits tumor growth in vivo. Conclusions: ARID2 suppressed the malignant advancement of CC by inactivating the TGF-β1/Smad pathway, providing valuable insights into the treatment of CC.