Crohn’s disease (CD) is a chronic, relapsing and incurable inflammatory disorder. MiRNAs, which modulate gene expression by binding to mRNAs, may make significant contributions to understanding the complex pathobiology and etiology of CD. This study aimed to investigate the therapeutic role and mechanism of miR-130a-3p in CD.
Differentially expressed miRNAs in colon tissues of CD patients and normal controls (NCs) were screened using a miRNA microarray and then validated by quantitative reverse transcriptase-PCR (qRT-PCR). The functional role of miR-130a-3p in the pathogenesis of CD was then demonstrated by in vitro and in vivo studies. The target genes of miR-130a-3p and the associated signaling pathways were identified using bioinformatics analysis and experimental verification of the interactions between the target predicted by the algorithms and dysregulated mRNAs. The therapeutic role of miR-130a-3p in trinitro-benzene-sulfonic acid (TNBS)-induced colitis models was further investigated.
Our data demonstrated that miR-130a-3p is the most significantly upregulated miRNA and that miR-130a KO significantly protects mice against TNBS-induced colitis. Gain- and loss-of-function studies indicated that miR-130a-3p promotes CD development by targetingATG16L1via the NF-κB pathway. Furthermore, a miR-130a-3p inhibitor significantly suppressed NLRP3 inflammasome activity by inducing autophagy in a mouse macrophage cell line (RAW264.7). Therapeutically, a miR-130a-3p inhibitor effectively ameliorated the severity of TNBS-induced colitis.
Our study reveals that miR-130a-3p promotes CD progression via the ATG16L1/NF-κB pathway and serves as a potential preclinical therapeutic target in CD.
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