Abstract
Lung cancer is a common cancer type, and has the highest mortality rate in the world. A genome‑wide association study suggests that the genetic marker rs9390123 is significantly associated with DNA repair capacity (DRC) in lung cancer. Analysis of the data derived from the 1000 Genomes Project indicated that there is another single nucleotide polymorphism (SNP), rs9399451, in strong linkage disequilibrium with rs9390123 in Caucasian individuals, thus suggesting that this SNP could be associated with DRC. However, the causal SNP and mechanism of DRC remain unclear. In the present study, dual luciferase assay results indicated that both SNPs are functional in lung cells. Through chromosome conformation capture, an enhancer containing the two functional SNPs was observed to bind the promoter of peroxisomal biogenesis factor 3 and phosphatase and actin regulator2 antisense RNA 1 (PHACTR2‑AS1). Knockdown of PHACTR2‑AS1 could significantly influence lung cell proliferation, colony formation, migration and wound healing, which verified that PHACTR2‑AS1 is a novel oncogene for lung cancer. Through chromatin immunoprecipitation, the transcription factor POU class2 homeobox 1 (POU2F1) was identified to bind to the surrounding segments of these two SNPs, and their interaction was investigated. The present study identified the mechanism via which rs9390123 and rs9399451 could influence DRC.
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