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Human umbilical cord blood mesenchymal stem cells-derived exosomal microRNA-503-3p inhibits progression of human endometrial cancer cells through downregulating MEST

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Abstract

Endometrial cancer (EC) is a group of epithelial malignant tumors that occur in the endometrium. The specific pathogenesis is not revealed, hence, the goal of this study was to investigate the influence of human umbilical cord blood mesenchymal stem cells (hUMSCs)-derived exosomal microRNA-503-3p (miR-503-3p) on human EC cells by mediating mesoderm-specific transcript (MEST). The binding relationship between MiR-503-3p and MEST was searched. HUMSCs were collected and exosomes (Exos) were isolated and identified. Human EC cell lines HEC-1B and RL95-2 were transfected with elevated miR-503-3p or silenced MEST vector or co-cultured with Exos to figure their roles in biological functions of EC cells. The in vitro effect of miR-503-3p, MEST, and Exos on EC cells was further verified in vivo. MEST was a target of miR-503-3p. Overexpression of miR-503-3p or reduction of MEST suppressed the biological functions of EC cells. Enhanced MEST expression mitigated the role of upregulated miR-503-3p on the growth of EC cells. HUMSCs-derived Exos suppressed EC cell growth, upregulated miR-503-3p-modified HUMSCs-derived Exos had a more obvious inhibitory effect on EC cell growth. The anti-tumor effect of elevated miR-503-3p, silenced MEST, and HUMSCs-derived Exos were verified in nude mice. This study highlights that hUMSCs-derived exosomal miR-503-3p inhibits EC development by suppressing MEST, which is of great benefit to EC therapy.

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Fig. 1: miR-503-3p is poorly expressed and targets MEST in EC cells.
Fig. 2: Overexpression of miR-503-3p or reduction of MEST inhibits the progression of HEC-1B cells.
Fig. 3: Upregulating MEST reverses the inhibitory effect of miR-503-3p on HEC-1B cells.
Fig. 4: Identification of hUMSCs.
Fig. 5: Identification of hUMSCs-derived Exos.
Fig. 6: HUMSCs-derived Exos containing miR-503-3p repress the progression of HEC-1B cells.
Fig. 7: Overexpressed exosomal miR-503-3p decreases tumor weight and volume of EC in vivo.

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Acknowledgements

This study was supported by Research on Key Technologies of Adipose Mesenchymal Stem Cells in the Treatment of Premature Ovarian Failure Related Diseases. (No. 20200708082YY).

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HZ finished study design; YJ and ZQ finished experimental studies; Yiang and Jing Jiang finished data analysis, and Ying Jiang finished manuscript editing. All authors read and approved the final manuscript.

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Correspondence to Hong Zhang.

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Pan, Y., Wang, X., Li, Y. et al. Human umbilical cord blood mesenchymal stem cells-derived exosomal microRNA-503-3p inhibits progression of human endometrial cancer cells through downregulating MEST. Cancer Gene Ther 29, 1130–1139 (2022). https://doi.org/10.1038/s41417-021-00416-3

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