Upregulated NORAD is implicated in apoptosis, inflammation, and oxidative stress in ulcerative colitis through the nuclear factor-κappaB signaling.

Abstract

Ulcerative colitis (UC) is a chronic inflammatory disease that affects the colon. It has been discovered that long non-coding RNA activated by DNA damage (NORAD) is upregulated in UC patient-derived serums, but its functional mechanism in UC has not been disclosed. Relative levels of NORAD in colonic mucosal tissues and TNF-α-stimulated human normal colonic mucosal cells (FHCs) were detected. Functional experiments were executed to evaluate the effects of NORAD silencing on TNF-α-induced FHC proliferation, apoptosis, inflammation, and oxidative stress. The molecular mechanism related to NORAD was predicted by starBase and confirmed by dual-luciferase reporter and RIP assays. Our data exhibited higher levels of NORAD in UC patient-derived colonic mucosal tissues and TNF-α-stimulated FHCs. Functional experiments presented that NORAD inhibition impaired TNF-α-induced FHC apoptosis, inflammation, and oxidative stress. NORAD acted as a miR-552-3p sponge, and miR-552-3p silencing weakened NORAD inhibition-mediated effects on TNF-α-induced FHC apoptosis, inflammation, and oxidative stress. Myeloid differentiation primary response gene 88 (MYD88) was verified as a miR-552-3p target, and MYD88 overexpression whittled miR-552-3p mimic-mediated inhibition on TNF-α-induced FHC apoptosis, inflammation, and oxidative stress. Notably, TNF-α-induced NORAD regulated the nuclear factor-κappaB (NF-κB) signaling via the miR-552-3p/MYD88 axis. NORAD participates in TNF-α-induced FHC apoptosis, inflammation, and oxidative stress via the NF-κB signaling via the miR-552-3p/MYD88 axis, offering new insights into the pathogenesis of UC.