Published online Dec 14, 2018. doi: 10.3748/wjg.v24.i46.5234
Peer-review started: September 4, 2018
First decision: October 4, 2018
Revised: October 31, 2018
Accepted: November 7, 2018
Article in press: November 8, 2018
Published online: December 14, 2018
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with an increasing prevalence. Pediatric IBD has severe phenotypes, but the etiology of IBD remains unknown. A number of studies have shown that microRNAs participate in the development of IBD and that miR-15a has an altered expression level in IBD patients, but the underlying mechanisms have not been fully elucidated. Cell division cycle (Cdc)42 is a Rho family small GTPase, and it has been reported that Cdc42 is critical for intestinal epithelial stem cell differentiation into a functional intestinal barrier. MicroRNA-Cdc42 signaling plays a role in some biological processes, and Target Scan identified a putative seed region of miR-15a in the wild-type 3’-UTR of Cdc42. Thus, we hypothesized that miR-15a regulates Cdc42 to disrupt the intestinal barrier in IBD development.
The main goal of this study is to find the role of microRNA-Cdc42 signaling in pediatric IBD development. Our study found that miR-15a negatively regulates intestinal epithelial junctions through Cdc42 in Caco-2 cells and in pediatric IBD. This finding will provide a critical clue for understanding IBD development in the future.
The objectives of this study were to determine whether Cdc42 is regulated by miR-15a in the development of pediatric IBD. Through our study, we found that miR-15a negatively regulates intestinal epithelial junctions through Cdc42 in Caco-2 cells and in pediatric IBD. This study provides a new clue for understanding the development of IBD and will help researchers study the etiology of IBD and provide new methods for IBD treatment in the future.
We cultured cells, used tumor necrosis factor (TNF)-α to stimulate cells, employed plasmids and lentiviruses to change miR-15a and Cdc42 expression, performed dual-luciferase assay, quantitative reverse transcription polymerase chain reaction and immunofluorescence. Statistical analysis was performed using t test of variance and Pearson’s r test of correlation using Graphpad Prism version 6.0.
We demonstrated that miR-15a negatively regulates intestinal epithelial junctions through Cdc42 in Caco-2 cells and pediatric IBD. This is believed to be the first study of the miR-15a-Cdc42 signaling pathway in pediatric IBD patients.
This study had some limitations. First, we found a correlation between miR-15a, Cdc42 and Pediatric Crohn’s Disease Activity Index, but the R values were not high, possibly due to the small number of patients. Second, we only included seven ulcerative colitis (UC) patients, which may be one of the reasons why we did not find altered miR-15a expression in UC patients. Last, we showed that miR-15a negatively regulates intestinal epithelial junctions through Cdc42, but we did not study how Cdc42 regulates intestinal epithelial junctions. This will be studied in our future research.
MiR-15a negatively regulates intestinal epithelial junctions through Cdc42 in pediatric IBD. This is believed to be the first study of the miR-15a - Cdc42 signaling pathway in pediatric IBD patients. Additionally, this study provides evidence that Cdc42 is a miR-15a target gene, and this will provide a critical clue for understanding IBD development, and may also provide new methods for future IBD treatments.
It is better get more patients, particularly UC patients. We will study how Cdc42 regulates intestinal epithelial junctions in our future research.