Polymorphism rs2395655 affects LEDGF/p75 binding activity and p21WAF1/CIP1 gene expression in esophageal squamous cell carcinoma

We demonstrated for the first time that LEDGF/p75 binds to STRE element implicated in polymorphism rs2395655 and regulates the p21 gene expression in ESCC cells and tissues. Our results suggested that the elevated p21 protein expression and rs2395655 GG variant may serve as positive prognostic factors for ESCC patients. Abstractp21WAF1/CIP1 (p21) plays critical roles in cell ‐cycle regulation and DNA repair and is transcriptionally regulated through p53‐dependent or ‐independent pathways. Bioinformatic analysis predicated one stress‐response element (STRE) implicated in single nucleotide polymorphism (SNP) rs2395655 of the p21 promoter. Here, we investigated the transcriptional regulatory function of rs2395655 variant genotype and analyzed its associations with the p21 expression and clinical outcomes in esophageal squamous cell carcinoma (ESCC) patients. Luciferase assay results showed significantly increased transcriptional activity of the rs2395655 G a llele‐containing p21 promoter compared with rs2395655 A allele‐containing counterpart, especially in ESCC cells with ectopic LEDGF/p75 expression. Furthermore electrophoretic mobility shift assay using the rs2395655 G or A allele‐containing probe and chromatin immunoprecipitation assay with s pecific anti‐LEDGF/p75 antibody indicated the potential binding activity of LEDGF/p75 with the STRE element implicated in rs2395655 G allele of the p21 promoter. Subsequent specific RNA interference‐mediated depleti...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research