Background
Colonic epithelial cell apoptosis and pyroptosis had a close relationship with the pathological progression of ulcerative colitis (UC). LncRNA play a crucial role in the progression of UC. However, the role of the lncRNA MALAT1 in colonic epithelial cell apoptosis and pyroptosis remains unclear.
Conclusions
These findings suggest that MALAT1 represents a promising therapeutic target for the treatment of UC by modulating the miR-22-3p/NLRP3 pathway, potentially leading to novel strategies for reducing inflammation and cell death in the colon.
Methods
UC colitis cell model was established through lipopolysaccharide (LPS) treatment. MiR-22-3p and MALAT1 expression in fetal human colon (FHC) cells were analyzed by qRT-PCR. Proliferation and apoptosis of FHCs were measured using CCK-8 assay and flow cytometry, respectively. Pyroptosis indicators including interleukin (IL)-1β, IL-18, tumor necrosis factor-α (TNF-α), NLR family pyrin domain containing 3 (NLRP3), caspase-1, and N-gasdermin D (N-GSDMD) in FHCs were detected using ELISA, qRT-PCR, western blotting, and immunofluorescence.
Results
In this study, apoptosis was facilitated, IL-1β, IL-18, and TNF-α levels were enhanced, NLRP3, caspase-1, N-GSDMD protein were increased, and MALAT1 expression was markedly increased in LPS-treated FHCs (LTFs). MALAT1 knockdown remarkably facilitated proliferation and suppressed apoptosis, reduced IL-1β, IL-18, and TNF-α levels, and decreased the protein of NLRP3, caspase-1, N-GSDMD. Furthermore, NLRP3 overexpression remarkably reversed the effect of MALAT1-downexpression in LTFs. In addition, miR-22-3p could bind with MALAT1 and NLRP3 3' UTR. Furthermore, miR-22-3p inhibition remarkably reversed the effect of MALAT1 overexpression in LTFs. Conclusions: These findings suggest that MALAT1 represents a promising therapeutic target for the treatment of UC by modulating the miR-22-3p/NLRP3 pathway, potentially leading to novel strategies for reducing inflammation and cell death in the colon.