Lim, Eun Bi Oh, Ho-Suk Kim, Kang Chang Kim, Moon-Ho Kim, Young Jin Kim, Bong Jo Nho, Chu Won Cho, Yoon Shin 2024-01-19T12:30:13Z 2024-01-19T12:30:13Z 2022-04-21 2022-04 1471-2164 https://pubs.kist.re.kr/handle/201004/115462 Background Colorectal cancer (CRC) is the third most common cancer worldwide and is influenced by environmental and genetic factors. Although numerous genetic loci for CRC have been identified, the overall understanding of the genetic factors is yet to be elucidated. We sought to discover new genes involved in CRC applying genetic association analysis and functional study. Results We conducted exome array analysis on 194 CRC and 600 control subjects for discovering new candidate CRC genes. Fisher&apos;s exact test detected one exome-wide significant functional locus for CRC on SMCO1 (P < 10(-6)) and two suggestive functional loci on HLA-C and NUTM1 (10(-6) <= P < 10(-4)). To evaluate the biological role of three candidate CRC genes, the differential expression of these genes between CRC and non-cancer colorectal cells was analyzed using qRT-PCR and publicly available gene expression data. Of three genes, HLA-C consistently revealed the significant down-regulation in CRC cells. In addition, we detected a reduction in cell viability in the HLA-C overexpression CRC cell line, implying the functional relevance of HLA-C in CRC. To understand the underlying mechanism exerted by HLA-C in CRC development, we conducted RNA sequencing analyses of HLA-C overexpression CRC cells and non-cancer colorectal cells. Pathway analysis detected that significantly down-regulated genes in HLA-C overexpression CRC cells were highly enriched in cancer-related signaling pathways such as JAK/STAT, ErbB, and Hedgehog signaling pathways. Conclusions Exome array CRC case-control analysis followed by functional validation demonstrated that HLA-C likely exerts its influence on CRC development via cancer-related signaling pathways. English BMC Identification and functional validation of HLA-C as a potential gene involved in colorectal cancer in the Korean population Article 10.1186/s12864-022-08509-5 1 BMC GENOMICS, v.23, no.1 BMC GENOMICS 23 1 Y scie scopus 000778028500006 Biotechnology & Applied Microbiology Genetics & Heredity Biotechnology & Applied Microbiology Genetics & Heredity Article GENOME-WIDE ASSOCIATION SUSCEPTIBILITY LOCI RNA-SEQ CLASS-I SCAN METAANALYSIS PROGNOSIS BIOLOGY TOOL Colorectal cancer Exome array association analysis Functional validation RNA sequencing