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MiRNA-29c-3p Promotes Intestinal Inflammation via Targeting Leukemia Inhibitory Factor in Ulcerative Colitis
Jian Guo1,2, Ruiya Zhang3, Yiqing Zhao3
1Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, 030006, People's Republic of China.
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 3'-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.
Insights
MicroRNA-29c-3p dysregulation promotes gut inflammation in ulcerative colitis by suppressing leukemia inhibitory factor (LIF). This study reveals miR-29c-3p/LIF axis modulation in inflammatory bowel disease pathogenesis.
Area of Science:
- Gastroenterology
- Molecular Biology
- Immunology
Background:
- Micro-RNAs (miRNAs) are implicated in inflammatory bowel diseases (IBD) pathogenesis.
- Specific functions of miRNAs in IBD, particularly ulcerative colitis (UC), remain underexplored.
- This study focuses on miR-29c-3p and its role in UC.
Purpose of the Study:
- To investigate the effect of miR-29c-3p in ulcerative colitis (UC).
- To identify and validate the target gene of miR-29c-3p in the context of UC.
- To elucidate the role of the miR-29c-3p/leukemia inhibitory factor (LIF) axis in intestinal inflammation.
Main Methods:
- Quantification of miR-29c-3p and LIF in UC patient tissues and a mouse colitis model using qRT-PCR and Western blotting.
- Bioinformatic prediction, luciferase reporter assays, and transfection experiments to confirm LIF as a target of miR-29c-3p.
- In vivo (experimental colitis mice) and in vitro (Caco-2 cells) assessments of the miR-29c-3p/LIF axis in intestinal inflammation.
Main Results:
- miR-29c-3p was downregulated, while LIF was upregulated in inflamed colon tissues from UC patients and DSS-induced colitis mice.
- miR-29c-3p directly targets and inhibits LIF expression by binding to its 3'-untranslated region.
- The miR-29c-3p/LIF axis influences inflammatory cytokine production, cell proliferation, and apoptosis; overexpression of miR-29c-3p aggravated experimental colitis by suppressing LIF.
Conclusions:
- Upregulation of miR-29c-3p promotes gut inflammation and pro-inflammatory mediator expression by suppressing LIF.
- The miR-29c-3p/LIF axis is a key modulator in the pathogenesis of ulcerative colitis.
- Targeting this axis may offer therapeutic strategies for UC.
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