miR-206 as a Biomarker for Response to Mesalamine Treatment in Ulcerative Colitis
Autor: | Carlos D. Minacapelli, Peter S. Amenta, Manisha Bajpai, Kiron M. Das, Xin Geng, James Van Gurp, Elizabeth Poplin, Steven R. Brant |
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Rok vydání: | 2018 |
Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Gastroenterology Young Adult 03 medical and health sciences 0302 clinical medicine Western blot Downregulation and upregulation Internal medicine microRNA Humans Immunology and Allergy Medicine Colitis Mesalamine Receptor Pathological medicine.diagnostic_test business.industry Anti-Inflammatory Agents Non-Steroidal Receptor Adenosine A3 Middle Aged Prognosis medicine.disease Ulcerative colitis MicroRNAs 030104 developmental biology Gene Expression Regulation Biomarker (medicine) Colitis Ulcerative Female 030211 gastroenterology & hepatology business HT29 Cells Biomarkers Follow-Up Studies |
Zdroj: | Inflammatory Bowel Diseases. 25:78-84 |
ISSN: | 1536-4844 1078-0998 |
Popis: | Background MicroRNAs (miRNAs) are important post-translational regulators. Elevated levels of miR-206 in ulcerative colitis (UC) were associated with suppression of anti-inflammatory A3 adenosine receptor (A3AR) expression. However, the relationship of miR-206 to histologic remission in UC patients remains unknown. This study correlates expression levels of miR-206 with histologic remission in patients treated via long-term mesalamine treatment to identify a possible mode of action for this mainstay drug for UC. Methods Expression of miR-206 and its target A3AR were analyzed in HT29 cell line before and after mesalamine treatment (2 mM) at different time points (0, 4, 12, and 24 hours) by qRT-PCR and western blot analysis. Expression of miR-206 and pathological scores of colonoscopic biopsy specimens were studied in 10 UC patients treated with mesalamine treatment for 2 to 6 years. Results miR-206 transcripts decreased 2.23-fold (P = 0.0001) 4 hours after 2 mM mesalamine treatment in HT29 colon cells compared with untreated controls. However, the mRNA/protein levels of A3AR increased by 4-fold (P = 0.04) and 2-fold, respectively, in same cells. miR-206 relative expression decreased significantly in patients treated with 4.8 g of mesalamine (P = 0.002) but not with 2.4 g (P = 0.35). Tissue assessment of sequential mesalamine-treated colonoscopic biopsies indicate a strong correlation between downregulation of miR-206 and histologic improvement (R = 0.9111). Conclusion Mesalamine treatment has an effect on epithelial miRNAs. Downregulation of miR-206 by long-term mesalamine treatment may confer a protective effect in inducing and maintaining histologic remission. Thus, miR-206 expression levels can be utilized as a possible biomarker for therapeutic response to mesalamine treatment. |
Databáze: | OpenAIRE |
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