MicroRNA Expression Profiling of Normal and Malignant Human Colonic Stem Cells Identifies

Authors

Vignesh Viswanathan, Helen F Graham Cancer Center and Research Institute
Lynn Opdenaker, Helen F Graham Cancer Center and Research Institute
Shirin Modarai, Helen F Graham Cancer Center and Research Institute
Jeremy Z Fields, CA*TX Inc
Gregory Gonye, Nanostring Technologies
Bruce M Boman, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

4-17-2020

Comments

This article is the author’s final published version in International Journal of Molecular Sciences, Volume 21, Issue 8, April 2020, Article number 2804.

The published version is available at https://doi.org/10.3390/ijms21082804. Copyright © Viswanathan et al.

Abstract

MicroRNAs (miRNAs) have a critical role in regulating stem cells (SCs) during development, and because aberrant expression of miRNAs occurs in various cancers, our goal was to determine if dysregulation of miRNAs is involved in the SC origin of colorectal cancer (CRC). We previously reported that aldehyde dehydrogenase (ALDH) is a marker for normal and malignant human colonic SCs and tracks SC overpopulation during colon tumorigenesis. MicroRNA expression was studied in ALDH-positive SCs from normal and malignant human colon tissues by Nanostring miRNA profiling. Our findings show that: (1) A unique miRNA signature distinguishes ALDH-positive CRC cells from ALDH-positive normal colonic epithelial cells, (2) Expression of four miRNAs (miRNA200c, miRNA92a, miRNA20a, miRNA93) are significantly altered in CRC SCs compared to normal colonic SCs, (3) miRNA92a expression is also upregulated in ALDH-positive HT29 CRC SCs as compared to ALDH-negative SCs, (4) miRNA92a targets the 3'UTR of LRIG1 SC gene, and (5) miRNA92a modulates proliferation of HT29 CRC cells. Thus, our findings indicate that overexpression of miRNA92a contributes to the SC origin of CRC. Strategies designed to modulate miRNA expression, such as miRNA92a, may provide ways to target malignant SCs and to develop more effective therapies against CRC.

Recommended Citation

Viswanathan, Vignesh; Opdenaker, Lynn; Modarai, Shirin; Fields, Jeremy Z; Gonye, Gregory; and Boman, Bruce M, "MicroRNA Expression Profiling of Normal and Malignant Human Colonic Stem Cells Identifies" (2020). Department of Pharmacology and Experimental Therapeutics Faculty Papers. Paper 121.
https://jdc.jefferson.edu/petfp/121

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

32316543

Language

English