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Volume 1

Journal of Blood Disorders and Treatment

World Hematology 2018

October 22-23, 2018

Page 15

Notes:

Hematology and Oncology Congress

October 22-23, 2018 Warsaw, Poland

10

th

World

Chronic colitis and colitis-associated colorectal carcinogenesis

T

he activation of Wnt/beta-catenin signaling pathway and chronic colitis malignant transformation are the two major

causes to colorectal cancer. The former is well studies, but the mechanisms of colitis develop and how chronic colitis

progress to malignance is largely unknown. Using a unique mouse model, we have demonstrated that the mice with targeted

disruption of the intestinal mucin gene

Muc2

spontaneously develop chronic inflammation at colon and rectum at early age,

whose histopathology was similar to ulcerative colitis in human. In the aged mice, Muc2-/- mice develop colonic and rectal

adenocarcinoma accompanying severe inflammation. To determine the mechanisms of the malignant transformation, we

conducted miRNA array on the colonic epithelial cells from Muc2-/- and +/+ mice. MicroRNA profiling showed differential

expression of miRNAs (i.e. lower or higher expression enrichments) in Muc2-/- mice. Based on relevance to cytokines and

cancer, themiRNAs were validated and were found significantly down-regulated or up-regulated in human colitis and colorectal

cancer tissues, respectively. The targets of the miRNAs were further characterized and their functions were investigated. More

studies from the Muc2-/- mice showed disorder of gut microbiota. Moreover, a novel tumor suppressor PRSS8 also plays a

critical role in colorectal carcinogenesis and progression, for instance, tissue-specific deletion of the PRSS8 gene resulted in

intestinal inflammation and tumor formation in mice. Gene set enrichment analysis showed that the colitis and tumorigenesis

were linked to the activationWnt/beta-catenin, PI3K/AKT and EMT (Epithelial-Mesenchymal Transition) signaling pathways.

Taken above, the disorder of gut microbiota could result in genetic mutations, epigenetic alterations and activation of oncogenic

signaling in colorectal epithelial cells, leading to colitis development, promoting malignant transformation and mediating

colorectal cancer metastasis.

Biography

Wancai Yang is the Dean of the Institute of Precision Medicine and School of Basic Medical Sciences, Jining Medical University, China and a Professor of Pathology,

University of Illinois at Chicago, USA. He is also an Adjunct Professor of Biological Sciences, University of Texas, El Paso, USA. He has obtained his MD degree and was

trained as a Pathologist from China and received his Postdoctoral training on Cancer Biology from Rockefeller University and Albert Einstein Cancer Center and then

worked as an Assistant Professor. In 2006, he moved to the Department of Pathology, University of Illinois at Chicago. His research focuses on the determination of mech-

anisms of gastrointestinal carcinogenesis, identification of biomarkers for cancer detection and patient selection for chemotherapy and implication of precision medicine in

cancers. He has published about 90 articles and has brought important impact in clinical significance.

wyang06@uic.edu

Wancai Yang

Jining Medical University, China

Wancai Yang, J Blood Disord Treat 2018, Volume 1