| Upregulation of Proapoptotic MicroRNA mir-125a After Massive Small Bowel Resection in Rats. | |
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MedLine Citation:
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PMID: 22418008 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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OBJECTIVE: : Short bowel syndrome remains a condition of high morbidity and mortality, and current therapeutic options carry significant side effects. To identify new treatments we focused on postresection changes in microRNAs-short noncoding RNAs, which suppress target genes--and suggest a previously undiscovered role for microRNA-125a (mir-125a) in intestinal adaptation. METHODS: : Rats underwent either 80% massive small bowel resection or transection and were harvested after 48 hours. Jejunum was harvested for microRNA microarrays, laser capture microdissection, and RNA and protein analysis. Mir-125a was overexpressed in intestinal epithelium-6 (crypt-derived) cells (IEC-6) and effects on proliferation and apoptosis determined using MTS and flow cytometry. Expression of potential targets of mir-125a in rat jejunum and IEC-6 cells was determined using quantitative real-time polymerase chain reaction (RNA) and Western blotting (protein). RESULTS: : Resection upregulated mir-125a and mir-214 by 2.4-folds and 3.2-folds, respectively. Highest levels of expression were noted in the crypt fraction. Mir-125a overexpression induced apoptosis and resultant growth arrest in IEC-6 cells. The expression of the prosurvival Bcl-2 family member Mcl-1 was downregulated in both mir-125a-overexpressing IEC-6 cells and in jejunum of resected rats, confirming Mcl-1 as a previously undiscovered target of mir-125a. CONCLUSIONS: : Upregulation of mir-125a suppresses the prosurvival protein Mcl1, producing the increase in apoptosis known to accompany the proliferative changes characteristic of intestinal adaptation. Our data highlight a potential role for microRNAs as mediators of the adaptive process and may facilitate the development of new therapeutic options for short bowel syndrome. |
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Authors:
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Anita Balakrishnan; Adam T Stearns; Peter J Park; Jonathan M Dreyfuss; Stanley W Ashley; David B Rhoads; Ali Tavakkolizadeh |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Annals of surgery Volume: 255 ISSN: 1528-1140 ISO Abbreviation: Ann. Surg. Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-03-15 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372354 Medline TA: Ann Surg Country: United States |
Other Details:
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Languages: eng Pagination: 747-53 Citation Subset: AIM; IM |
Affiliation:
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*Departments of Surgery, Brigham and Women's Hospital, Boston, MA †School of Clinical Sciences, Division of Gastroenterology, University of Liverpool, Liverpool, United Kingdom ‡Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, United Kingdom §Center for Biomedical Informatics, Harvard Medical School, Boston, MA ¶Medicine, Brigham and Women's Hospital, Boston, MA ‖Pediatric Endocrine Unit, Mass-General Hospital for Children, Boston, MA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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