title: Sam68 modulates apoptosis of intestinal epithelial cells via mediating NF-κB activation in ulcerative colitis.
abstract: Sam68 (Src-associated substrate during mitosis of 68 KDa), also known as KHDRBS1 (KH domain containing, RNA binding, signal transduction associated 1), belongs to the prototypic member of the signal transduction activator of RNA (STAR) family of RNA-binding proteins. Sam68 is implicated in various cellular processes including RNA metabolism, apoptosis, signal transduction. Previous researches demonstrated that Sam68 regulated nuclear transcription factor kappa B (NF-κB) to induce inflammation. However, the expression and biological functions of Sam68 in ulcerative colitis (UC) are not clear. In this study, we reported for the first time that Sam68 was up-regulated in intestinal epithelial cells (IECs) of patients with UC. In DSS-induced mouse colitis model, we observed the overexpression of Sam68 accompanied with increased levels of IEC apoptotic markers (active caspase-3 and cleaved PARP) and NF-κB activation indicators (p-p65 and p-IκB) in colitis IECs. Co-localization of Sam68 with active caspase-3 (and p-p65) in IECs of the DSS-induced colitis group further indicated the possible involvement of NF-κB-mediated IEC apoptosis. Applying TNF-α-treated HT-29 cells as an in vitro IEC inflammation model, we confirmed the positive correlation amomg Sam68, NF-κB activation and caspase-dependent apoptosis. Immunofluorescence and immunoprecipitation assay identified nuclear translocation and physical interaction of Sam68 and NF-κB subunits in TNF-α-treated HT-29 cells. Besides, depletion of Sam68 by RNA interference greatly alleviated NF-κB activation and apoptosis in TNF-α-treated HT-29 cells. Taken together, our results indicated that Sam68 modulates apoptosis of intestinal epithelial cells via mediating NF-κB activation in UC.
authors.affiliation: Department of Digestion Medicine, Affiliated Yixing Hospital of Jiangsu University, 75 Tongzhenguan Road, Yixing 214200, Jiangsu, People's Republic of China.
authors.forename: Ji
authors.initials: J
authors.lastname: Qian
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu, People's Republic of China.
authors.forename: Weijuan
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu, People's Republic of China.
authors.forename: Xianjing
authors.initials: X
authors.lastname: Miao
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu, People's Republic of China. Electronic address: larry017@163.com.
authors.forename: Liren
authors.initials: L
authors.lastname: Li
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D019073:HT29 Cells; D006801:Humans; D047468:Immunoprecipitation; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C489559:KHDRBS1 protein, human; D016328:NF-kappa B; D016601:RNA-Binding Proteins
keywords: Apoptosis; Intestinal epithelial cell; NF-κB; Sam68; Ulcerative colitis