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

Abstract

Background 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. Methods 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. Results 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. Conclusion 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.

LncRNA-CBR3-AS1 promotes and enhances the malignancy of ulcerative colitis via targeting miRNA-145-5p/FN1

“…Yang W discovered that the PI3K pathway was used by ln-cRNA H19 to control UC (28). The lncRNA NORAD was also up-regulated in UC and used NF-κB to induce inflammation (29). However, just a little amount of study has been done to analyze the function of the lncRNA CBR3-AS1 in UC.…”

Crypts in Asymmetric Branching in Patients With Ulcerative Colitis in Remission

“…Is it because new CAB were not generated in UCR, or because CAB were generated, but at a slower pace than in LLUC? There was no indication that the failure to replicate more CAB in UCR was the result of crypt abrogation by apoptosis (20,21). Since similar abnormal crypt branching is not found in the normal colorectal mucosa in adults (17), the presence CAB in the colonic mucosa in adult patients with UC substantiates the notion that these crypts are genuine pathologic aberrations of cryptogenesis.…”

The regulation of lncRNAs and miRNAs in SARS-CoV-2 infection

“…22 lncRNAs with the ability to target the 10 cytokines overexpressed in the COVID-19 cytokine storm were found by Morenikeji et al, eight of which target two or more cytokines (Morenikeji et al, 2021). For instance, NORAD specifically targets five crucial cytokines (IL-6, IL-10, CSF3, CXCL10, and TNF-α), and its possible mechanisms may be the involvement of the NF-κB signaling pathway through the miR-552-39/MYD88 axis in TNF-α induced apoptosis, inflammatory, and oxidative stress (Lei et al, 2022), which in turn leads to an increase in multiple cytokines. RAD51-AS1 targets three significant cytokines (IL-6, TNF-α, CCL2), and its possible mechanisms may express in response to cellular damage from viral replication within macrophages in SARS-CoV-2 infection, leading to the expression of pro-inflammatory cytokines (Morenikeji et al, 2021).…”

“…The secretion of various cytokines during infection is closely related to clinical manifestations and cytokine storm is closely associated with ARDS and MOD (Sun et al, 2020). The breakthrough infection rate for SARS-CoV-2 has increased since the Omicron variant became mainstream (Wang X. et al, 2022). Therefore, we must advance our understanding of the infection mechanisms of SARS-CoV-2 and develop a new generation of therapeutic medicines and vaccines.…”