English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

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’s exact test detected one exome-wide significant functional locus for CRC on  SMCO1  ( P  &lt; 10 –6 ) and two suggestive functional loci on  HLA-C  and  NUTM1  (10 –6  ≤  P  &lt; 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.

Identification and functional validation of HLA-C as a potential gene involved in colorectal cancer in the Korean population