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MicroRNA hsa-let-7e-5p in hUC-MSC-EVs alleviates oral mucositis by targeting TAB2
Shuting Lin1, Dong Lai1, Yan Tian1
1Department of Transfusion, Central Laboratory, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, China.
Abstract:
Oral mucositis (OM) is a severe side effect of anti-cancer therapy, with limited available treatments. Mesenchymal stem cells (MSCs) and their secreted extracellular vesicles (EVs) have demonstrated effective protection against OM. However, the underlying mechanism remains elusive. In the current study, we purified EVs secreted by human umbilical cord MSCs (hUC-MSC-EVs) and investigated their role in lipopolysaccharide (LPS)-induced human oral keratinocytes (HOKs). We observed that treatment with hUC-MSC-EVs significantly reduced the inflammatory response of HOKs to LPS induction. Through small RNA-seq using miRNAs extracted from hUC-MSC-EVs, we identified hsa-let-7e-5p as one of the most highly expressed miRNAs. Bioinformatic analysis data indicated that hsa-let-7e-5p may inhibit the NF-κB signalling pathway by targeting TAB2. Overexpression of the hsa-let-7e-5p inhibitor significantly attenuated the anti-inflammatory effect of hUC-MSC-EVs in LPS-induced HOKs, which could be reversed by the knockdown of TAB2. In addition, we administered hUC-MSC-EVs in a hamster model for OM and observed that these EVs alleviated OM phenotypes. Taken together, our observations suggest that hsa-let-7e-5p in hUC-MSC-EVs could protect the oral mucosa from OM by repressing TAB2 expression.
Insights
Mesenchymal stem cell extracellular vesicles (EVs) show promise for treating oral mucositis (OM). These EVs, specifically hUC-MSC-EVs, reduce inflammation by delivering hsa-let-7e-5p, which targets TAB2 and the NF-κB pathway.
Area of Science:
- Biomedical research
- Stem cell biology
- Molecular medicine
Background:
- Oral mucositis (OM) is a debilitating side effect of cancer therapy with few treatment options.
- Mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) show potential for OM treatment, but mechanisms are unclear.
Purpose of the Study:
- To investigate the protective mechanism of human umbilical cord MSC-derived EVs (hUC-MSC-EVs) against lipopolysaccharide (LPS)-induced oral mucositis.
- To identify specific molecules within hUC-MSC-EVs responsible for their therapeutic effects.
Main Methods:
- Purification of hUC-MSC-EVs and treatment of LPS-induced human oral keratinocytes (HOKs).
- Small RNA sequencing (miRNA-seq) to identify key miRNAs in hUC-MSC-EVs.
- Bioinformatic analysis to predict miRNA targets and pathways.
- In vivo studies using a hamster model of OM.
Main Results:
- hUC-MSC-EV treatment significantly reduced inflammation in LPS-induced HOKs.
- hsa-let-7e-5p was identified as a highly expressed miRNA in hUC-MSC-EVs.
- hsa-let-7e-5p targets TAB2 and inhibits the NF-κB pathway, mediating the anti-inflammatory effects.
- hUC-MSC-EVs alleviated OM symptoms in a hamster model.
Conclusions:
- hUC-MSC-EVs protect against oral mucositis by delivering hsa-let-7e-5p.
- hsa-let-7e-5p exerts its protective effect by targeting TAB2 and suppressing the NF-κB signaling pathway.
- These findings highlight a novel therapeutic mechanism for OM using MSC-derived EVs.
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