miR-106b Fine Tunes ATG16L1 Expression and Autophagic Activity in Intestinal Epithelial HCT116 Cells
| Autor: | Zili Zhai, John H. Kwon, Feng Wu, Alice Y. Chuang |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Low protein
Blotting Western ATG5 Autophagy-Related Proteins Biology Real-Time Polymerase Chain Reaction Article ATG12 Autophagy Tumor Cells Cultured Humans Immunology and Allergy RNA Messenger 3' Untranslated Regions ATG16L1 Cell Proliferation Regulation of gene expression Reverse Transcriptase Polymerase Chain Reaction MRNA cleavage Gastroenterology BECN1 Cell biology Gene Expression Regulation Neoplastic MicroRNAs Colonic Neoplasms Carrier Proteins |
| Zdroj: | Inflammatory Bowel Diseases. 19:2295-2301 |
| ISSN: | 1078-0998 |
| DOI: | 10.1097/mib.0b013e31829e71cf |
| Popis: | MicroRNAs (miRNAs) are small RNA molecules that regulate over 30% of human protein-coding genes by binding to the 3'UTR of mRNAs that results in mRNA cleavage and/or translational arrest.1, 2 A single miRNA can regulate hundreds of genes simultaneously and an mRNA may be subject to regulation by multiple miRNAs coordinately.1 Based on the miRBase database, over 1000 mature human miRNAs have been identified so far.3 Therefore, miRNAs constitute a complex regulatory network in managing almost each physiological and pathological process. The dysregulated miRNAs have implicated in human diseases, including inflammatory bowel disease (IBD).4 We have previously reported that several miRNAs, including miR-106a, are differentially expressed in tissues of IBD patients.5-7 We are interested in assessing whether these dysregulated miRNAs are involved in the IBD pathogenesis. miR-106a belongs to the miR-17 family, which includes miRs-17, −20a, −20b, −93, and −106b. These miRNAs share the same seed region and therefore may target common mRNAs.8 An in silico analysis reveals that the members of miR-17 family target over 12 autophagy genes (Table, Supplemental Digital Content 1, http://links.lww.com/IBD/A217) such as ULK1, BECN1, ATG12, ATG5, and ATG16L1. These genes act sequentially in the autophagy process, with most of them involved in the autophagosome formation, a central event in autophagy;9 in particular, ATG12, ATG5, and ATG16L1 constitute an important protein conjugation system required for the autophagosome formation.10 In addition, miR-17 family members are predicted to target some signaling molecules that orchestrate autophagy activation, including PTEN, STAT3, and MAPK1. Therefore, miR-17 family miRNAs may play an integral role in regulating autophagic function by targeting diverse autophagy genes and autophagy regulators at once. Among the IBD-associated miRNAs, miR-106a especially attracted our attention because it is predicted to target ATG16L1, a genetic susceptibility gene for Crohn's disease (CD). Human data support a strong association of ATG16L1 T300A polymorphism with CD.11-13 Animal studies have demonstrated that ATG16L1 defect or low protein expression increases inflammatory response and produces CD-like pathology.14-16 Cumulated evidence suggests that autophagy in the intestinal epithelium behaves as a defensive strategy for clearance of microbes,17-19 but autophagy impairment results in intestinal epithelial dysfunction and IBD pathogenesis. In this study, we assessed the regulatory effects of miR-106a and other members of miR-17 family on ATG16L1 expression and autophagic activity in human intestinal epithelial HCT116 cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|