Long non-coding RNA GAS5 regulates the inflammatory response in inflammatory bowel disease via targeting the miR-23a-3p/BVES axis

Introduction:
Inflammatory bowel disease (IBD) is an inflammatory pathological condition for which effective drugs are currently lacking. The objective of this study was to reveal the regulatory mechanisms of growth arrest specific transcript 5 (GAS5) in IBD.

Material and methods:
To mimic IBD in vitro, human fetal colon (FHC) cells were exposed to lipopolysaccharide (LPS) to induce inflammation. The MTT method and flow cytometry were utilized to detect cell viability and apoptosis, respectively. Enzyme-linked immunosorbent assay was performed to determine cytokine concentrations. A luciferase reporter kit was utilized to confirm the binding between GAS5 and the microRNA miR-23a-3p, and between vascular epicardial substance (BVES) and miR-23a-3p.

Results:
GAS5 and BVES were lowly expressed in the colonic mucosal tissues obtained from patients with IBD, while miR-23a-3p was abundantly expressed. Both GAS5 upregulation and miR-23a-3p inhibition promoted proliferation, impeded apoptosis and abolished inflammatory cytokine release in FHC cells. The expression levels of miR-23a-3p and GAS5 and those of BVES and miR-23a-3p in the colonic mucosa of IBD patients were negatively correlated. GAS5 decreased the level of miR-23a-3p via direct targeting. BVES was targeted and suppressed by miR-23a-3p. Lastly, GAS5 promoted FHC cell proliferation, impeded apoptosis and inhibited cytokine release by upregulating BVES.

Conclusions:
GAS5 promoted cell viability, impeded apoptosis, and inhibited inflammation in colonic mucosal cells exposed to LPS by targeting miR-23a-3p and then promoting BVES expression. These findings imply that GAS5 could be further explored as a target for IBD.