+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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



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



Cancer Medicine 2019



p21WAF1/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 allele-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 specific 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 depletion or ectopic expression of LEDGF/p75 caused obviously down- or up-regulated expression of p21 mRNA in ESCC cells harboring rs2395655 GG genotype but not cells with rs2395655 AA genotype. Furthermore, rs2395655 GG genotype carriers showed significantly elevated p21 protein expression and conferred survival advantage in both univariate and multivariate analyses in total 218 ESCC patients. Our findings suggest that LEDGF/p75 regulates the p21 expression in ESCC cells through interacting with STRE element implicated in polymorphism rs2395655 and the elevated p21 protein expression and rs2395655 GG genotype may serve as positive prognostic factors for ESCC patients.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 066575115

Download citation: RISBibTeXText

PMID: 30854807

DOI: 10.1002/cam4.2067


Related references

Expression of cell cycle related proteins cyclin D1, p53 and p21WAF1/Cip1 in esophageal squamous cell carcinoma. Yi Chuan 32(5): 455-460, 2010

p21Waf1/Cip1 expression is a prognostic marker in curatively resected esophageal squamous cell carcinoma, but not p27Kip1, p53, or Rb. Annals of Surgical Oncology 6(5): 481-488, 1999

Expression of p21WAF1/CIP1, p53, bcl-2 and Ki-67 in venous leg ulcers with and without squamous cell carcinoma. Acta Dermato-Venereologica 80(4): 251-255, 2000

p21WAF1/CIP1 expression is a marker of poor prognosis in oral squamous cell carcinoma. Journal of Oral Pathology & Medicine 34(5): 274-279, 2005

Topological analysis of p21WAF1/CIP1 expression in esophageal squamous dysplasia. Clinical Cancer Research 6(2): 541-550, 2000

Expression of p21WAF1/CIP1 is unrelated to p53 tumour suppressor gene status in oral squamous cell carcinomas. Oral Oncology 34(3): 198-203, 1998

Differential activity of sulindac metabolites against squamous cell carcinoma of the head and neck is mediated by p21waf1/cip1 induction and cell cycle inhibition. Cancer Biology and Therapy 6(1): 30-39, 2006

Differential activity of sulindac metabolites against squamous cell carcinoma of the head and neck is mediated by p21waf1/cip1 induction and cell cycle inhibition. Cancer Biology & Therapy 6(1): 30-39, 2007

Experimental gene therapy using p21Waf1 gene for esophageal squamous cell carcinoma by gene gun technology. International Journal of Molecular Medicine 14(4): 545-551, 2004

Novel polymorphism in p21waf1/cip1 cyclin dependent kinase inhibitor gene: Association with human esophageal cancer. Oncogene 19(3): 323-328, Jan 20, 2000

Esophageal cancer in Chinese population: No polymorphism in codon 149 of P21Waf1/Cip1 cyclin dependent kinase gene. Oncogene 21(50): 7745-7748, 31 October, 2002

Expression of p21WAF1/CIP1 and p53 proteins in gastric carcinoma: Its relationships with cell proliferation activity and prognosis. Cancer Letters 170(2): 183-189, September 20, 2001

Expression and prognostic relevance of p21WAF1 in stage III esophageal squamous cell carcinoma. Diseases of the Esophagus 25(1): 67-71, 2012

Association between a microRNA-214 binding site polymorphism in the methylenetetrahydrofolate reductase gene and esophageal squamous cell carcinoma. Genetics and Molecular Research 15(2), 2017

p53 and p21WAF1/CIP1 overexpression at the invasive front of lower lip squamous cell carcinoma. Journal of Oral Pathology and Medicine 36(2): 88-92, 2007