rs9390123 and rs9399451 influence lung cancer DNA repair capacity by regulating the expression of PEX3 and PHACTR2-AS1 instead of PHACTR2

This article was originally published here

Oncol Rep. 2022 Mar;47(3):59. doi: 10.3892/ou.2022.8270. Published online January 21, 2022.


Lung cancer is a common type of cancer 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 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 may be associated with the DRC. However, the causal SNP and mechanism of the DRC remain unclear. In the present study, the results of the dual luciferase assay indicated that both SNPs are functional in lung cells. Through chromosomal conformation capture, an enhancer containing both functional SNPs was observed to bind to the peroxisome biogenesis factor 3 promoter and phosphatase and actin regulator antisense RNA 1 2 (PHACTR2‑AS1). Reversal of PHACTR2‑AS1 could significantly influence lung cell proliferation, colony formation, migration and wound healing, which has been verified that PHACTR2‑AS1 is a new oncogene for lung cancer. Through chromatin immunoprecipitation, the transcription factor POU class 2 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 by which rs9390123 and rs9399451 could influence the DRC.

PMID:35059740 | DOI: 10.3892/ou.2022.8270

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