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Hitendra S. Solanki Jayshree Advani Munish Kumar Prashant Kumar Hemant Bhagat T.S. Keshava Prasad David Sidransky Harsha Gowda Aditi Chatterjee

Abstract

Smoking and environmental pollutants are one of the major risk factors associated with bladder cancer. It is reported that one-half of the bladder cancer cases are directly linked to smoking habits. Second hand smoke also known as passive smoke or environmental tobacco smoke has been also associated with bladder cancer. Till date no systemic study has been done to compare the molecular alterations between direct and passive form of cigarette smoke in bladder cells. Using cell line model we studied the direct and vapor effect (passive smoke) of cigarette smoke condensate (CSC) in non-neoplastic bladder uroepithelial cells SV-HUC-1. We carried out microarray-based miRNA expression profiling of SV-HUC-1 cells chronically exposed to CSC and its vapor for 6 months compared to the parental cells. We identified downregulation of 28 miRNAs and upregulation of 12 miRNAs exclusively in vapor exposed cells, whereas 103 miRNAs were downregulated and 7 were upregulated exclusively in the cells directly treated with CSC. Further, miRNA-mRNA based pathway analysis led to the enrichment of distinct pathways in each condition. However, mRNA targets of differentially expressed miRNA from both conditions are associated with various biological processes involved in cell proliferation, epithelial-mesenchymal transition, actin cytoskeletal modelling and DNA damage response. This study reveals impact of CSC and its vapor on miRNA expression pattern in bladder epithelial cells. It provides mechanistic insights into miRNA expression changes that might be associated with oncogenic transformation of bladder epithelial cells.

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