Regulation of ATG16L1 by miR-142-3p in organoids.

Verpalen, I. (Inez) (2015) Regulation of ATG16L1 by miR-142-3p in organoids. thesis, Medicine.

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Abstract

Inflammatory Bowel Disease (IBD) is a family of chronic, relapsing, idiopathic disorders affecting the gastrointestinal tract. The pathogenesis of this disease is not well characterized. Genetic studies have implicated autophagy as a pathway whose dysfunction can lead to IBD, specifically through the impaired function or regulation of the autophagy genes NOD2 and ATG16L1. Evidence derived from work in cancer cell lines identified the microRNA miR- 142-3p as a regulator of ATG16L. However, these monoculture cell lines do not adequately recreate the complexity of the intestinal epithelia. To determine if miR-142-3p affects autophagy in a more physiologically relevant context, intestinal organoids were transduced with a lentiviral construct containing the miR-142-3p. These organoids and controls were stimulated with rapamycin or starvation media in order to induce autophagy and the autophagy markers ATG16L1 and LC3-II were assessed by Western blotting. The results demonstrated a reduction in autophagy in the miR-142-3p-transduced organoids compared to controls, further supporting the role of miR-142-3p as a regulator of autophagy. Understanding the interaction between miR-142-3p and ATG16L1 will further characterize the regulatory network driving autophagy in the intestinal epithelia, which can contribute to our wider understanding of the molecular basis of IBD. Determining the modulators of disease, such miR-142-3p, will generate new putative targets for the development of personalized therapeutics.

Item Type:	Thesis (Thesis)
Supervisor name:	Jones, N.L. and Bodewes, F.A.J.A.
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:56
Last Modified:	25 Jun 2020 10:56
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/1641

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