Sajiv Sethi, MD1, Jade Edwards, MD2, Anmol Warman3, Carla Duffoo, DO2, Niketa Patel, PhD2, Gitanjali Vidyarthi, MD2
1University of South Florida Morsani College of Medicine, Tampa, FL; 2James A. Haley Veterans' Hospital, Tampa, FL; 3Duke University, Durham, NC
Introduction: Colorectal cancer is the third most cancer diagnosed in USA. Long noncoding RNAs (lncRNAs) are important orchestrators of essential biological networks and regulate cell growth, apoptosis, epigenetics transcription and translation. Multiple lines of evidence link regulatory lncRNAs to diseases (Ref 1-2)
Methods: The project determined the expression of lncRNAs in samples from normal and highly aggressive colorectal cancer.
Using paraffin imbedded samples, the epithelial layer was demarcated under the microscope and isolated with a scalpel. Total RNA was isolated and cDNA was used in the LncProfiler qPCR Array (SBI).
Results: Results show an increase in lncRNAs DISC2, HAR1A, HAR1B, HULC, NEAT1, NRON, PRINS and RNCR3 in the cancer samples compared to the normal.
We further sought to evaluate whether an obese environment could promote the normal colon cells into cancer-like phenotype. To evaluate this, we used exosomes derived from adipose stem cells (ASC) obtained from lean or normal individuals to mimic the obese environment. Colon epithelial cells were cultured and either treated with lean ASC exosomes or obese exosomes for 24 hours. Total RNA was isolated and cDNA was used in the LncProfiler qPCR Array. Amongst the detected lncRNAs, our results showed an increase in DISC-2, NEAT1, NRON, PRINS and RNCR3 lncRNAs which were observed to be increased in the colon cancer samples.
Simultaneously, using real time qPCR we saw an increase in pro-survival genes Bcl2, Bcl-xL and caspase 9b in cells treated with exosomes from obese ASC
Discussion: The results suggest that obesity may lead to increased incidence of colon cancer. We have known it for years for obesity to increase the risk od colorectal cancers slightly and now we have some insights into the pathophysiology.
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Citation: Sajiv Sethi, MD; Jade Edwards, MD; Anmol Warman; Carla Duffoo, DO; Niketa Patel, PhD; Gitanjali Vidyarthi, MD. P1031 - LONG NONCODING RNAS (LNCRNAS) ARE DIFFERENT IN POLYPS OF OBESE AND LEAN SUGGESTING DIFFERENT PATHOPHYSIOLOGY. Program No. P1031. ACG 2019 Annual Scientific Meeting Abstracts. San Antonio, Texas: American College of Gastroenterology.