MiRNA-29c-3p Promotes Intestinal Inflammation via Targeting Leukemia Inhibitory Factor in Ulcerative Colitis

Abstract

Background: Dysregulation of micro-RNAs (miRNAs) is profoundly linked to inflammatory bowel diseases (IBD), but little is known about the specific biological functions of miRNAs in IBD. This study sought to elucidate the effect and the underlying target of miR-29c-3p in ulcerative colitis (UC). Methods: The levels of miR-29c-3p and leukemia inhibitory factor (LIF) were measured in inflamed lesions of UC patients and dextran sulfate sodium (DSS)-induced colitis mice by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. MiR-29c-3p was predicted to target LIF by bioinformatics software, which was verified via luciferase reporter assay and transfection of miR-29c-3p mimics or inhibitor. The role of miR-29c-3p/ LIF axis in intestinal inflammation was explored in experimental colitis mice and Caco-2 cells. Results: MiR-29c-3p was markedly downregulated while LIF was upregulated in colon tissues of UC patients and DSS-challenged colitis mice as well as in primary intestinal epithelial cells (IECs) and LPS-treated Caco-2 cells. MiR-29c-3p inhibited LIF expression at the transcriptional level via binding to LIF 3ʹ-untranslated region (UTR) in Caco-2 cells. Targeting miR-29c-3p/LIF axis regulated inflammatory cytokines production, cell proliferation and apoptosis. Overexpression of miR-29c-3p aggravated mice experimental colitis via suppressing LIF. Conclusion:Our findings demonstrate that the upregulation of miR-29c-3p promotes gut inflammation and the expression of pro-inflammatory mediators via suppressing LIF, thereby modulating the pathogenesis of UC.

A Proof-of-Concept Analysis of Plasma-Derived Exosomal microRNAs in Interstitial Pulmonary Fibrosis Secondary to Antisynthetase Syndrome

“…miR-29c is also implicated in the positive regulation of NK cells cytotoxicity [ 13 ], and, through the negative regulation of tumor necrosis factor alpha-induced protein 3 (TNFAIP3), it also modulates the activity of NF-kappa B in T cells [ 14 ]. Interestingly, miR-29c is upregulated in experimental models of sepsis [ 15 ] and ulcerative colitis [ 16 ], thus confirming its proinflammatory activity. Moreover, miR-29c seems to also display an antifibrotic action [ 17 ] through different mechanisms, such as the modulation of the Fer expression [ 18 ], and the blockade of the macrophage migration inhibitory factor [ 19 ].…”

Modulation of the Inflammatory Response in Polycystic Ovary Syndrome (PCOS)—Searching for Epigenetic Factors

“…Another miRNA considered in the context of the PCOS pathomechanism, miR-29c-3p, shows opposite effects with respect to inflammation, depending on the tissue and signaling pathways used. Hence, miR-29c-3p may promote intestinal inflammation by targeting leukemia inhibitory factor (LIF) in ulcerative colitis and, through targeting the transcription factor forkhead box protein O3 (FOXO3A), may ameliorate inflammatory damage of cells by NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome inhibition [ 197 , 198 , 199 ]. Moreover, miR-29c-3p participates in insulin function by targeting FOXO3A.…”

Protective role of circRNA CCND1 in ulcerative colitis via miR-142-5p/NCOA3 axis

“…Studies have found that many miRNAs are involved in the development of many diseases by post-translational regulation [ 15 , 16 ]. Recently, a number of studies regarding miRNAs in UC have reported a critical role of miRNAs during the development of UC, such as miR-182-5p [ 17 ] and miR-29c-3p [ 18 ]. Additionally, miRNA-142-5p is involved in cervical cancer [ 19 ].…”