Different effection of p.1125Val>Ala and rs11954856 in APC on Wnt signaling pathway

2017 
// Fei-Feng Li 1, 2, * , Zhi-Xun Zhao 3, * , Peng Yan 3 , Song Wang 3 , Zheng Liu 4 , Qiong Zhang 5 , Xiao-Ning Zhang 5 , Chang-Hao Sun 6 , Xi-Shan Wang 3,4 , Gui-Yu Wang 2, 3 and Shu-Lin Liu 1, 2, 7 1 Systemomics Center, College of Pharmacy, and Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, China 2 Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Heilongjiang, China 3 Department of Colorectal Surgery of the Second Affiliated Hospital, Harbin Medical University, Harbin, China 4 Department of Colorectal Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China 5 Department of Antibiotics, Heilongjiang Province Food and Drug Inspection Testing Institute, Harbin, China 6 Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China 7 Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Canada * These authors have contributed equally to this work Correspondance to: Gui-Yu Wang, email: guiywang@gmail.com Shu-Lin Liu, email: slliu@ucalgary.ca Xi-Shan Wang, email: wxshan1208@126.com Keywords: colorectal cancer, APC, mutation, Wnt/β-catenin signaling pathway, gene expression Received: May 04, 2017      Accepted: May 23, 2017      Published: August 05, 2017 ABSTRACT Colorectal cancer (CRC) is among the most common and fatal forms of solid tumors worldwide and more than two thirds of CRC and adenomas patients have APC gene mutations. APC is a key regulator in the Wnt/β-catenin signaling pathway but its roles in CRC remains to be elucidated. In this study, we compared APC genes between CRC patients and controls to determine possible associations of nucleotide changes in the APC gene with the pathways involved in CRC pathogenesis. All participants received physical and enteroscopic examinations. The APC gene was sequenced for 300 Chinese Han CRC patients and 411 normal controls, and the expression levels of genes in the signaling pathway were analyzed using Western Blotting. Statistical analyses were conducted using SPSS (version 19.0) software. We found that rs11954856 in the APC gene was associated with colorectal cancer and could increase the expression levels of APC , β-catenin , TCF7L1 , TCF7L2 and LEF1 genes in the pathway in the CRC patients, demonstrating the involvement of APC in the pathological processes leading to CRC.
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