Abstract 22: RECQ1 promotes the expression of genes significantly associated with cancer progression

Abstract

Abstract RecQ helicases (represented by five homologs in humans: RECQ1, WRN, BLM, RECQ4, and RECQ5) are vital to maintain genomic stability under replication stress and germ line mutations in WRN, BLM and RECQ4 are associated with cancer predisposition syndromes. Expression of RECQ1 has been associated with the process of cellular transformation and over-expression of RECQ1 has been reported in a variety of human cancers. Furthermore, siRNA-mediated knockdown of RECQ1 has a cancer cell specific effect in cell culture models and also suppresses tumor growth in mouse xenografts including lung, liver, pancreatic and colorectal cancer. In a panel of 60 human cancer cell lines (NCI-60), we have found that RECQ1 mRNA expression positively correlates with the mesenchymal marker Vimentin and negatively correlates with epithelial markers such as KRT8. We also observed significant positive correlation of RECQ1 expression with Vimentin and epithelial to mesenchymal transition (EMT) promoting proteins and negative correlation with CDH1 (epithelial marker) in cancer patient samples from TCGA (The Cancer Genome Atlas). Importantly, quantitative real-time PCR analyses in a set of 16 colorectal cancer patient samples revealed strong positive correlation of RECQ1 expression with Vimentin. Furthermore, lower expression of RECQ1 significantly correlated with better prognosis of recurrence-free survival in breast and ovarian cancer patients. Global analyses of gene expression upon knockdown of RECQ1 in HeLa (cervical adenocarcinomas) and MDA-MB-231 (breast adenocarcinoma) cells identified a subset of genes involved in cell invasion, migration and adhesion as most robustly regulated by RECQ1. Consistent with this result, we demonstrate that knockdown of RECQ1 significantly inhibits cell migration and invasion. These findings identify a novel function of RECQ1 in regulation of gene expression and suggest that RECQ1 contributes to tumor development and progression, in part, through regulating the expression of key genes that promote invasion and metastasis of cancer cells. Additionally, our data suggests that RECQ1 expression may serve as predictive marker of clinical outcome. Citation Format: Xing Lu, Xiao Ling Li, Swetha Parvathaneni, Ashish Lal, Sudha Sharma. RECQ1 promotes the expression of genes significantly associated with cancer progression. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Susceptibility and Cancer Susceptibility Syndromes; Jan 29-Feb 1, 2014; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(23 Suppl):Abstract nr 22. doi:10.1158/1538-7445.CANSUSC14-22