Open AccessMiR‐3130‐5p is an intermediate modulator of 2q33 and influences the invasiveness of lung adenocarcinoma by targeting NDUFS1
Author(s) -
Zhan Juan,
Sun Shenghua,
Chen Yixing,
Xu Chaoqun,
Chen Qinwei,
Li Minjie,
Pei Yihua,
Li Qiyuan
Publication year - 2021
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.3885
Subject(s) - expression quantitative trait loci , carcinogenesis , lung cancer , biology , microrna , adenocarcinoma , genome wide association study , cancer research , phenotype , quantitative trait locus , genetics , gene , cancer , oncology , single nucleotide polymorphism , medicine , genotype
Genome‐wide association studies (GWAS) have reported a handful of loci associated with lung cancer risk, of which the pathogenic pathways are largely unknown. We performed cis ‐expression quantitative trait loci (eQTL) mapping for 376 lung cancer related GWAS loci in 227 TCGA lung adenocarcinoma (LUAD) and reported two risk loci as eQTL of miRNA. Among the miRNAs in association with lung cancer risk, we further predicted and validated miR‐3130‐5p as an intermediate modulator of risk loci 2q33 and the tumor suppressor NDUFS1. We assessed the phenotypic impacts of the interaction between miR‐3130‐5p and NDUFS1 in both lung cancer cell lines and mice xenograft models. As a result, miR‐3130‐5p directly regulates the expression of NDUFS1 and the corresponding tumor invasiveness, migration and epithelial‐mesenchymal transition (EMT). Our findings provide important clues for the pathogenic mechanism of 2q33 in lung carcinogenesis which informs clinical diagnosis and prognosis of LUAD. We performed a cis ‐eQTL analysis for 376 lung cancer risk loci based on the expression profiles of 251 miRNAs in a cohort of 227 TCGA lung adenocarcinoma. We report a novel pathogenic pathway of 2q33 via miR‐3130‐5p and NDUFS1.