Fibrinolytic factors promote inflammatory colonic carcinogenesis through miR- 126-mediated targeting of the proteolytic niche

Joint Event on 4^th International Conference on Molecular Medicine and Diagnostics & 26^th Cancer Genomics Congress: New Era for Cancer Prevention & International Conference on Biomarkers and Clinical Research

July 15-16, 2019 Abu Dhabi, UAE

Yousef Salama

An-Najah National University, Palestine

Scientific Tracks Abstracts: J Mol Biomark Diagn

Abstract :

Inflammation is a well-established driver of carcinogenesis and inflammatory bowel disease patients have an increased risk of developing Colorectal Cancer (CRC). We found high intratumoral expression of the fibrinolytic factor Tissue-type Plasminogen Activator (tPA) in human colorectal tissues. Using the azoxymethane/dextran sodium sulfate-induced inflammation-associated colon carcinogenesis model, we demonstrate that tPA and plasmin are up-regulated during colon carcinogenesis. Genetic and pharmacological inhibition of plasmin or tPA suppressed inflammation-induced tumor formation in AOM/DSS induced mice. Mechanistically, tPA downregulated AP2a and miR-126 by activating NF-kB signaling. Furthermore, tPA via miR126 deregulates factors like HB-EGF, proteases (tPA or MMP9) and CCL2 that are known to promote inflammation-induced CRC. Taken together, our study indicates that targeting plasmin may be useful in the prevention of colon cancer in individuals with inflammatory bowel disease.

Biography :

Yousef Salama has completed his PhD from the Institute of Medical Sciences, University of Tokyo, Japan. He is currently working as a Professor at An-Najah National University, School of Medicine. He has published more than 25 papers in reputed journals in the field of cancer and stem cell research.

E-mail: yousef.ut@gmail.com