MicroRNA hsa‐let‐7e‐5p in hUCMSCEVs alleviates oral mucositis by targeting TAB2

Author:

Lin Shuting1,Lai Dong1,Tian Yan1,Lai Fei1,Long Min1,Ji Changfu1,Hao Gengxin2ORCID

Affiliation:

1. Department of Transfusion Central Laboratory, The Second Affiliated Hospital of Xiamen Medical College Xiamen China

2. College of Ocean Food and Biological Engineering Jimei University Xiamen China

Abstract

AbstractOral 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.

Publisher

Wiley

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