Abstract
Detection of colorectal dysplasia during surveillance colonoscopy remains the best method of determining risk for colitis-associated colorectal cancer (CAC). miRNAs (miRs) show great promise as tissue-specific biomarkers of neoplasia. The goal of this study was to explore the miR expression profile of precancerous dysplastic lesions in the AOM/DSS mouse model and identify early molecular changes associated with CAC. Epithelial cells were laser-microdissected from the colonic mucosa (inflamed versus dysplastic) of mice with AOM/DSS-induced colitis. A miR signature that can distinguish inflamed non-neoplastic mucosa from dysplasia was identified. Bioinformatic analyses led to the discovery of associated miR gene targets and enriched pathways and supported the construction of a network interaction map. miR-1a-3p was one of the miRs with the highest number of predicted targets, including Cdk6. Interestingly, miR-1a-3p and Cdk6 were down- and up-regulated in dysplastic lesions, respectively. Transfection of HCT116 and RKO cells with miR-1a-3p mimics induced apoptosis and cell cycle arrest in G1, suggesting its biological function. A slight reduction in the level of CDK6 transcripts was also observed in cells transfected with miR-1. These data provide novel insight into the early molecular alterations that accompany the development of CAC and identify a miR signature that represents a promising biomarker for the early detection of colitis-associated dysplasia.
Original language | English |
---|---|
Article number | 13024 |
Journal | International Journal of Molecular Sciences |
Volume | 23 |
Issue number | 21 |
DOIs | |
State | Published - Sep 27 2022 |
Keywords
- colitis
- colitis-associated colon cancer
- early detection
- microRNAs
Fingerprint
Dive into the research topics of 'Dysregulation of miR-1-3p: An Early Event in Colitis-Associated Dysplasia'. Together they form a unique fingerprint.Equipment
-
Biostatistics and Bioinformatics Facility
Ross, PhD, ScM, E. A. (Director), Devarajan, PhD, K. (Staff), Zhou, PhD, Y. (Staff), Zhou, MSE, PhD, Y. (Staff), Egleston, PhD, MPP, B. (Staff), Hasler, PhD, J. S. (Staff) & Zhang, PhD, L. (Staff)
Equipment/facility: Facility
-
Cell Culture Facility
Campbell, PhD, K. S. (Director) & Kwok, PhD, T. (Manager)
Equipment/facility: Facility
-
Cell Sorting Facility
Campbell, PhD, K. S. (Director), Font-Burgada, PhD, J. (Director), MacFarlane, PhD, A. (Manager) & Oesterling, BS, J. (Manager)
Equipment/facility: Facility