Overexpression of family with sequence similarity 134, member B (FAM134B) in colon cancers and its tumor suppressive properties in vitro

Abstract

This study aims to investigate the overexpression-induced properties of tumor suppressor <i>FAM134B</i> (family with sequence similarity 134, member B) in colon cancer, examine the potential gene regulators of <i>FAM134B</i> expression and its impact on mitochondrial function. <i>FAM134B</i> was overexpressed in colon cancer and non-neoplastic colonic epithelial cells. Various cell-based assays including apoptosis, cell cycle, cell proliferation, clonogenic, extracellular flux and wound healing assays were performed. Western blot analysis was used to confirm and identify potential interacting partners of <i>FAM134B in vitro</i>. Immunohistochemistry and qPCR were employed to determine the expressions of MIF and <i>FAM134B</i>, respectively, on 63 patients with colorectal carcinoma. Results showed that <i>FAM134B</i> is involved in the cell cycle and mitochondrial function of colon cancer. Overexpression of <i>FAM134B</i> was coupled with increased expression levels of APC, p53, and MIF. Increased expression of both APC and p53 further validates the potential role of tumor suppressor <i>FAM134B</i> in regulating cancer progression through the WNT/ß-catenin signaling pathway. In approximately 70% of the patients with colorectal cancer, <i>FAM134B</i> downregulation was correlated with MIF protein overexpression while the remaining 30% showed concurrent expression of <i>FAM134B</i> and MIF (<i>P</i> = .045). High expression of MIF coupled with low expression of <i>FAM134B</i> is associated with microsatellite instability status in colorectal carcinomas (<i>P</i> = .049). <i>FAM134B</i> may exert its tumor suppressive function through affecting cell cycle, mitochondrial function via potentially interacting with MIF and p53.