Work

Correction: VILIP-1 Downregulation in Non-Small Cell Lung Carcinomas: Mechanisms and Prediction of Survival

Year: 2013

Type: erratum

Abstract: VILIP-1, a member of the neuronal Ca++ sensor protein family, acts as a tumor suppressor gene in an experimental animal model by inhibiting cell proliferation, adhesion and invasiveness of squamous cell carcinoma cells.Western Blot analysis of human tumor cells showed that VILIP-1 expression was undetectable in several types of human tumor cells, including 11 out of 12 non-small cell lung carcinoma (NSCLC) cell lines.The down-regulation of VILIP-1 was due to loss of VILIP-1 mRNA transcripts.Rearrangements, large gene deletions or mutations were not found.Hypermethylation of the VILIP-1 promoter played an important role in gene silencing.In most VILIP-1-silent cells the VILIP-1 promoter was methylated.In vitro methylation of the VILIP-1 promoter reduced its activity in a promoter-reporter assay.Transcriptional activity of endogenous VILIP-1 promoter was recovered by treatment with 59-aza-29-deoxycytidine (59-Aza-dC).Trichostatin A (TSA), a histone deacetylase inhibitor, potently induced VILIP-1 expression, indicating that histone deacetylation is an additional mechanism of VILIP-1 silencing.TSA increased histone H3 and H4 acetylation in the region of the VILIP-1 promoter.Furthermore, statistical analysis of expression and promoter methylation (n = 150 primary NSCLC samples) showed a significant relationship between promoter methylation and protein expression downregulation as well as between survival and decreased or absent VILIP-1 expression in lung cancer tissues (p,0.0001).VILIP-1 expression is silenced by promoter hypermethylation and histone deacetylation in aggressive NSCLC cell lines and primary tumors and its clinical evaluation could have a role as a predictor of short-term survival in lung cancer patients.

Source: PLoS ONE

DOI: 10.1371/annotation/ad0e4775-c4d5-454c-96c0-755ba9fcc806