Literature DB >> 33708425

miR-4477b gene as a novel pathogenic mutation occurring during the transformation of colorectal adenoma into colorectal cancer.

Xiaoyu He1, Guohua Cheng1, Feng Xiao1, Lei Zhang1, Gang Jin1, Xin Zhao1, Ying Liu1, Juan Liang1, Yarong Li1, Zhaoyu Liu1, Qiang Yuan1, Hongwei Ren1, Qilong Wu1, Jinrong Wu1, Lili Xue1, Jing Feng1, Zhihui Wang1, Yueming Xing1, Wei Wu1, Zheng Li1, Dong Wei1, Xiang Song1.   

Abstract

BACKGROUND: Polyps may develop into colorectal cancer (CRC) after 10-20 years. The occurrence of polyps and tumors caused by somatic gene mutations is considered a main pathogenesis of CRC. Among all general patients with polyps or CRC, some had adenoma of varying degrees that were consistent with familial colorectal adenomas. A patient with CRC (the propositus) and his brothers and sister, all of whom had varying degrees of colorectal polyps showed different adenomas with different members in a family.
METHODS: In the present study, a total of 9 family members were investigated, and a family tree was drawn. Genomic DNA was extracted from peripheral venous blood samples from family members, and whole-exome sequencing (WES) and Sanger sequencing were performed on the DNA samples. The result of WES was compared with compared directly to the reference genome (hg19) with Burrows-Wheeler Aligner, which is as control group from.
RESULTS: We identified a base substitution in the miR-4477b gene (c.68415368T>G, chromosome 9 q13), predicted the target gene of miR-4477b through the biologic website, and analyzed the Gene Ontology (GO) and signal pathway of the target gene. The GO functional annotation analysis of the target gene of mir4477b revealed that these genes are involved mainly in the G1/S transition of the mitotic cell cycle, activation of mitogen-activated protein kinase activity, protein phosphorylation, and membrane, centrosome, cytoplasm, zinc ion-binding, protein-binding, and ligase activity. Kyoto Encyclopedia of Gene and Genomes pathway analysis revealed that miR-4477b regulates target genes mainly involved in the phosphoinositide 3-kinase/Akt signaling pathway, regulation of the actin cytoskeleton, proteoglycans in cancer, pathways in cancer, and renal cell carcinoma.
CONCLUSIONS: The mutation of the has-mir-4477b gene likely leads to the occurrence of adenoma and CRC. In-depth studies of patients from the same family with different stages of adenoma can avoid errors caused by gene diversity, incomplete clinical data, and uncertain disease development. The has-mir-4477b gene may represent a key gene mutation in colorectal carcinogenesis and a multiyear cancer risk for patients that requires further attention. 2021 Journal of Gastrointestinal Oncology. All rights reserved.

Entities:  

Keywords:  bioinformatics analysis; colorectal cancer (CRC); colorectal polyp; miR-4477b; mutation; phosphoinositide 3-kinase

Year:  2021        PMID: 33708425      PMCID: PMC7944151          DOI: 10.21037/jgo-20-600

Source DB:  PubMed          Journal:  J Gastrointest Oncol        ISSN: 2078-6891


  36 in total

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