Identification of cis- and trans-acting elements regulating calretinin expression in mesothelioma cells

Calretinin (CALB2) is a diagnostic marker for epithelioid mesothelioma. It is also a prognostic marker since patients with tumors expressing high calretinin levels have better overall survival. Silencing of calretinin decreases viability of epithelioid mesothelioma cells. Our aim was to elucidate me...

Full description

Saved in:
Bibliographic Details
Published in:Oncotarget 2016-04, Vol.7 (16), p.21272-21286
Main Authors: Kresoja-Rakic, Jelena, Kapaklikaya, Esra, Ziltener, Gabriela, Dalcher, Damian, Santoro, Raffaella, Christensen, Brock C, Johnson, Kevin C, Schwaller, Beat, Weder, Walter, Stahel, Rolf A, Felley-Bosco, Emanuela
Format: Article
Language:English
Subjects:
Base Sequence
Calbindin 2 - genetics
Calbindin 2 - metabolism
Cells, Cultured
E2F2 Transcription Factor - genetics
E2F2 Transcription Factor - metabolism
Gene Expression Regulation, Neoplastic
Humans
Mesothelioma - genetics
Mesothelioma - metabolism
Mesothelioma - pathology
Nuclear Respiratory Factor 1 - genetics
Nuclear Respiratory Factor 1 - metabolism
Promoter Regions, Genetic - genetics
Regulatory Sequences, Nucleic Acid
Research Paper
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Calretinin (CALB2) is a diagnostic marker for epithelioid mesothelioma. It is also a prognostic marker since patients with tumors expressing high calretinin levels have better overall survival. Silencing of calretinin decreases viability of epithelioid mesothelioma cells. Our aim was to elucidate mechanisms regulating calretinin expression in mesothelioma. Analysis of calretinin transcript and protein suggested a control at the mRNA level. Treatment with 5-aza-2'-deoxycytidine and analysis of TCGA data indicated that promoter methylation is not likely to be involved. Therefore, we investigated CALB2 promoter by analyzing ~1kb of genomic sequence surrounding the transcription start site (TSS) + 1 using promoter reporter assay. Deletion analysis of CALB2 proximal promoter showed that sequence spanning the -161/+80bp region sustained transcriptional activity. Site-directed analysis identified important cis-regulatory elements within this -161/+80bp CALB2 promoter. EMSA and ChIP assays confirmed binding of NRF-1 and E2F2 to the CALB2 promoter and siRNA knockdown of NRF-1 led to decreased expression of calretinin. Cell synchronization experiment showed that calretinin expression was cell cycle regulated with a peak of expression at G1/S phase. This study provides the first insight in the regulation of CALB2 expression in mesothelioma cells.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.7114