LncRNA regulation in mouse lung tumor from dibenzo[def,p]chrysene induced carcinogenesis in a transplacental Nrf2 knockout mouse model

Dibenzo[def,p]chrysene (DBC) is a highly potent, but less prevalent, environmental carcinogen belonging to a class of compounds known as Polycyclic Aromatic Hydrocarbons (PAHs). They are highly ubiquitous and arise as a byproduct of natural and anthropogenic combustion processes. Previous studies have documented carcinogenic effects upon in utero exposure of PAHs. Nuclear Factor Erythroid-2-Related Factor (Nrf2) is a transcription factor vital to the oxidative stress response. Consequently, Nrf2 deficiency in animal models has shown increased tumor incidence compared to those with Nrf2 when treated with an environmental carcinogen. \ud The primary objective of this study is to analyze the up or down regulation of various long non-coding RNA (lncRNA >200bp) utilizing a Nrf2 Knockout Mouse Model. LncRNA have been found to possess a myriad of functions as molecular signals and molecular decoys that move to suppress gene expression. They have the ability to guide ribonucleoprotein complexes to assemble at specific chromatin sites. Consequently, cis or trans gene expression is induced. \ud For this study, control lung and lung tumor tissue archived from previous studies were analyzed for their lncRNA expression profile. The two treatment groups (male Nrf2+/- ) utilized are as follow: control lung from 10-month old offspring; Lung tumor tissue from 10-month old offspring born to mothers treated with DBC. Total RNA was isolated from lung tissue and lung tumor tissue. A commercially available LncProfiler qtPCR array (System Biosciences, Mountain View, CA. #RA930A-1) was used to examine the lncRNA profiles of the treatment group relative to the control. These results are in the process of being obtained and will become available for viewing during this year’s CUE undergraduate research symposium. This study is being conducted in efforts to document a potential correlation between fetal exposure to PAHs and up regulation of cancer associated lncRNA as well as stem cell depletion. This data is intended to be a segway into future investigations of the same type with more detailed emphasis on Indole-3-Carbinol (I3C) and Sulforaphane (SFN) intervention, chemoprotective agents present in cruciferous vegetables. Such agents have been shown to selectively induce apoptosis and decrease tumor burden in animals treated with PAHs