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A large-scale microRNA transcriptome-wide association study identifies two susceptibility microRNAs, miR-1307-5p and miR-192-3p, for colorectal cancer risk

Authors
 Zhishan Chen  ;  Weiqiang Lin  ;  Qiuyin Cai  ;  Sun-Seog Kweon  ;  Xiao-Ou Shu  ;  Chizu Tanikawa  ;  Wei-Hua Jia  ;  Ying Wang  ;  Xinwan Su  ;  Yuan Yuan  ;  Wanqing Wen  ;  Jeongseon Kim  ;  Aesun Shin  ;  Sun Ha Jee  ;  Keitaro Matsuo  ;  Dong-Hyun Kim  ;  Nan Wang  ;  Jie Ping  ;  Min-Ho Shin  ;  Zefang Ren  ;  Jae Hwan Oh  ;  Isao Oze  ;  Yoon-Ok Ahn  ;  Keum Ji Jung  ;  Yu-Tang Gao  ;  Zhi-Zhong Pan  ;  Yoichiro Kamatan  ;  Weidong Han  ;  Jirong Long  ;  Koichi Matsuda  ;  Wei Zheng  ;  Xingyi Guo 
Citation
 HUMAN MOLECULAR GENETICS, Vol.33(4) : 333-341, 2024-02 
Journal Title
HUMAN MOLECULAR GENETICS
ISSN
 0964-6906 
Issue Date
2024-02
MeSH
Cell Proliferation / genetics ; Colorectal Neoplasms* / metabolism ; Gene Expression Regulation, Neoplastic / genetics ; Genome-Wide Association Study ; HCT116 Cells ; Humans ; MicroRNAs* / genetics ; MicroRNAs* / metabolism ; Transcriptome / genetics
Keywords
TWAS ; colorectal cancer ; miR-1307-5p ; miR-192-3p ; microRNA
Abstract
Transcriptome-wide association studies (TWAS) have identified many putative susceptibility genes for colorectal cancer (CRC) risk. However, susceptibility miRNAs, critical dysregulators of gene expression, remain unexplored. We genotyped DNA samples from 313 CRC East Asian patients and performed small RNA sequencing in their normal colon tissues distant from tumors to build genetic models for predicting miRNA expression. We applied these models and data from genome-wide association studies (GWAS) including 23 942 cases and 217 267 controls of East Asian ancestry to investigate associations of predicted miRNA expression with CRC risk. Perturbation experiments separately by promoting and inhibiting miRNAs expressions and further in vitro assays in both SW480 and HCT116 cells were conducted. At a Bonferroni-corrected threshold of P < 4.5 × 10-4, we identified two putative susceptibility miRNAs, miR-1307-5p and miR-192-3p, located in regions more than 500 kb away from any GWAS-identified risk variants in CRC. We observed that a high predicted expression of miR-1307-5p was associated with increased CRC risk, while a low predicted expression of miR-192-3p was associated with increased CRC risk. Our experimental results further provide strong evidence of their susceptible roles by showing that miR-1307-5p and miR-192-3p play a regulatory role, respectively, in promoting and inhibiting CRC cell proliferation, migration, and invasion, which was consistently observed in both SW480 and HCT116 cells. Our study provides additional insights into the biological mechanisms underlying CRC development.
Full Text
https://academic.oup.com/hmg/article/33/4/333/7333894
DOI
10.1093/hmg/ddad185
Appears in Collections:
4. Graduate School of Public Health (보건대학원) > Graduate School of Public Health (보건대학원) > 1. Journal Papers
Yonsei Authors
Jung, Keum Ji(정금지) ORCID logo https://orcid.org/0000-0003-4993-0666
Jee, Sun Ha(지선하) ORCID logo https://orcid.org/0000-0001-9519-3068
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/198153
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