Dysregulation of miR-1-3p: An Early Event in Colitis-Associated Dysplasia

Mariana F. Fragoso, Geysson J. Fernandez, Lisa Vanderveer, Harry S. Cooper, Michael Slifker, Margie L. Clapper

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 languageEnglish
Article number13024
JournalInternational Journal of Molecular Sciences
Volume23
Issue number21
DOIs
StatePublished - Sep 27 2022

Keywords

  • colitis
  • colitis-associated colon cancer
  • early detection
  • microRNAs

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