Dataset Information

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 FAM134B (family with sequence similarity 134, member B) in colon cancer, examine the potential gene regulators of FAM134B expression and its impact on mitochondrial function. FAM134B 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 FAM134B in vitro. Immunohistochemistry and qPCR were employed to determine the expressions of MIF and FAM134B, respectively, on 63 patients with colorectal carcinoma. Results showed that FAM134B is involved in the cell cycle and mitochondrial function of colon cancer. Overexpression of FAM134B 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 FAM134B in regulating cancer progression through the WNT/ß-catenin signaling pathway. In approximately 70% of the patients with colorectal cancer, FAM134B downregulation was correlated with MIF protein overexpression while the remaining 30% showed concurrent expression of FAM134B and MIF (P = .045). High expression of MIF coupled with low expression of FAM134B is associated with microsatellite instability status in colorectal carcinomas (P = .049). FAM134B may exert its tumor suppressive function through affecting cell cycle, mitochondrial function via potentially interacting with MIF and p53.

SUBMITTER: Lee KT

PROVIDER: S-EPMC7583494 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Solute carrier family 7 member 2 (SLC7A2, also known as CAT2) is an inducible transporter of the semi-essential amino acid L-arginine (L-Arg), which has been implicated in wound repair. We have reported that both SLC7A2 expression and L-Arg availability are decreased in colonic tissues from inflammatory bowel disease patients and that mice lacking Slc7a2 exhibit a more severe disease course when exposed to dextran sulfate sodium (DSS) compared to wild-type (WT) mice. Here, we present evidence that SLC7A2 plays a role in modulating colon tumorigenesis in the azoxymethane (AOM)-DSS model of colitis-associated carcinogenesis (CAC). SLC7A2 was localized predominantly to colonic epithelial cells in WT mice. Utilizing the AOM-DSS model, Slc7a2-/- mice had significantly increased tumor number, burden, and risk of high-grade dysplasia vs. WT mice. Tumors from Slc7a2-/- mice exhibited significantly increased levels of the proinflammatory cytokines/chemokines IL-1β, CXCL1, CXCL5, IL-3, CXCL2, CCL3, and CCL4, but decreased levels of IL-4, CXCL9, and CXCL10 compared to tumors from WT mice. This was accompanied by a shift toward pro-tumorigenic M2 macrophage activation in Slc7a2-deficient mice, as marked by increased colonic CD11b+F4/80+ARG1+ cells with no alteration in CD11b+F4/80+NOS2+ cells by flow cytometry and immunofluorescence microscopy. The shift toward M2 macrophage activation was confirmed in bone marrow-derived macrophages from Slc7a2-/- mice. In bone marrow chimeras between Slc7a2-/- and WT mice, the recipient genotype drove the CAC phenotype, suggesting the importance of epithelial SLC7A2 in abrogating neoplastic risk. These data reveal that SLC7A2 has a significant role in the protection from CAC in the setting of chronic colitis, and suggest that the decreased SLC7A2 in inflammatory bowel disease (IBD) may contribute to CAC risk. Strategies to enhance L-Arg availability by supplementing L-Arg and/or increasing L-Arg uptake could represent a therapeutic approach in IBD to reduce the substantial long-term risk of colorectal carcinoma.

Dataset Information

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets