Date of Award

1-1-2013

Document Type

Open Access Dissertation

Department

Biomedical Science

First Advisor

Elizabeth A Murphy

Abstract

Colorectal cancer remains the third most common malignancy and the fourth most common cause of cancer mortality worldwide. Dysregulated miRNA levels are associated with several types of malignancies and may serve as important biomarkers and/or therapeutic targets in colorectal cancer. We examined the role of miRNA-155 on tumorigenesis and associated symptoms using a well-characterized mouse model of colorectal cancer. C57BL/6 wild-type mice and miRNA-155-/- mice (n=7-13 group) were given a single injection of AOM (10mg/Kg) followed by 3 cycles of DSS (2% in the water for 1 week followed by 2 weeks of plain water). A C57BL/6 wild-type group that did not receive AOM/DSS treatment was also included as a comparison (n=5). Mice were monitored twice weekly for body weight changes and symptom severity. Prior to sacrifice, body composition measurements were taken. At sacrifice, colon tissue, spleen, and adipose tissue were harvested. miRNA-155-/- mice had significantly fewer tumors than wild-type mice. In addition, miRNA-155-/- mice exhibited a lower symptom severity score and a greater body weight gain than wild-type mice over the course of the experiment. In general, wild-type mice had a reduction in fat mass and percent body fat as well as fat pad weights compared to the disease-free controls but miRNA-155 completely offset this effect. If these findings can be clinically translated, miRNA-155 may lead to an effective clinical biomarker and/or therapeutic target in colorectal cancer.

Share

COinS