MicroRNA Expression Profiling of Normal and Malignant Human Colonic Stem Cells Identifies miRNA92a as a Regulator of the LRIG1 Stem Cell Gene
| Autor: | Shirin R. Modarai, Gregory E. Gonye, Lynn M. Opdenaker, Vignesh Viswanathan, Jeremy Z. Fields, Bruce M. Boman |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Colorectal cancer
Regulator Aldehyde dehydrogenase crypts Catalysis Article Inorganic Chemistry lcsh:Chemistry Downregulation and upregulation stem cells microRNA medicine Humans miRNA92a human Physical and Theoretical Chemistry Molecular Biology Gene 3' Untranslated Regions lcsh:QH301-705.5 Spectroscopy Membrane Glycoproteins biology integumentary system Gene Expression Profiling Organic Chemistry LRIG1 colon General Medicine medicine.disease digestive system diseases Computer Science Applications Up-Regulation Gene expression profiling Gene Expression Regulation Neoplastic MicroRNAs nervous system lcsh:Biology (General) lcsh:QD1-999 Case-Control Studies biology.protein Cancer research Neoplastic Stem Cells Stem cell Colorectal Neoplasms HT29 Cells tissues |
| Zdroj: | International Journal of Molecular Sciences, Vol 21, Iss 2804, p 2804 (2020) International Journal of Molecular Sciences Volume 21 Issue 8 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | 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&prime 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. |
| Databáze: | OpenAIRE |
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