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MiR-192-5p-Modified Tumor-Associated Macrophages-Derived Exosome Suppressed Endometrial Cancer Progression Through Targeting IRAK1/NF-κB Signaling

  • Endometrium: Original Article
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Abstract

Tumor-associated macrophages (TAMs) are a major regulator in the development of endometrial cancer (EC). It was indicated that TAMs could crosstalk with cancer cells via transferring exosomes which carrying microRNAs (miRNAs). Firstly, we found that TAMs could promote the epithelial-mesenchymal transition (EMT) of EC cells and inhibit its apoptosis. Next, we further found that TAMs regulated the EMT and apoptosis of EC cells through transferring exosomes into EC cells. Then, lowly expressed miR-192-5p in TAMs-derived exosomes was proved. Moreover, our data demonstrated that upregulation of miR-192-5p in TAMs-derived exosomes could significantly promote the apoptosis of EC cells and impede its EMT. IRAK1 was proved to be a downstream target of miR-192-5p. Importantly, we indicated that miR-192-5p-overexpressed TAMs-derived exosomes regulated the EC cells apoptosis and EMT through inhibiting IRAK1/NF-κB signaling pathway. In addition, we also revealed that overexpression of miR-192-5p in TAMs-derived exosomes obviously limits the growth of tumors. Overall, in TAMs-derived exosomes, our data demonstrated that overexpression of miR-192-5p could effectively suppress the progression of EC. Our data provid a new target for EC treatment.

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Data sharing is not applicable to this article as no new data were created or analyzed in this study.

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Funding

This study was supported by the Inner Mongolia Autonomous Region People’s Hospital Fund (2019YN12) and Inner Mongolia Medical University million project joint project (YKD2018KJBW(LH)061).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Inner Mongolia People’s Hospital, 20 Zhaowuda Road, Saihan District, Hohhot City, Inner Mongolia, China

    Yilin Wang, Hongsheng Ma & Rina Su

  2. Hohhot Maternal and Child Health Care Hospital, 33 Baotou Street, Yuquan District, Hohhot City, Inner Mongolia, China

    Yajie Li

Authors
  1. Yilin Wang
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  2. Hongsheng Ma
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  4. Rina Su
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Contributions

Conceptualization: Yilin Wang and Hongsheng Ma; methodology: Yilin Wang, Yajie Li and Hongsheng Ma; formal analysis and investigation: Yilin Wang and Rina Su; writing (original draft preparation): Yilin Wang; writing (review and editing): Hongsheng Ma, Yajie Li, and Rina Su; funding acquisition: Hongsheng Ma; resources: Hongsheng Ma; supervision: Yilin Wang, Hongsheng Ma, Yajie Li, and Rina Su.

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Correspondence to Hongsheng Ma.

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The approval of the animal experiment was granted by the Ethics Committee of Inner Mongolia People’s Hospital.

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Supplementary Information

Supplementary Figure 1.

Detection of M2 macrophage-related cytokines. (A-C) The expression of Arg-1 mRNA, IL-10 mRNA and IL-4 mRNA in THP-1 cells (Ctrl group), M0 and TAMs was determined using qRT-PCR. *P < 0.05 compared with Ctrl group. (PNG 101 kb)

High Resolution (TIF 186 kb)

Supplementary Figure 2.

Effect of TAMs-derived exosomes on EC cells EMT. EC cells were treated with PBS, M0-conditional medium, and TAMs-conditional medium. Then, (A) western blot was executed to detect the expression of ZEB1 and N-cadherin. *P < 0.05 compared with Ctrl group. (B) Immunofluorescence was performed to detect the expression of E-cadherin and Vimentin in EC cells. (PNG 1460 kb)

High Resolution (TIF 4001 kb)

Supplementary Figure 3.

Detection of the cell proliferation of EC cells. (A) EC cells were treated with PBS, M0-conditional medium, and TAMs-conditional medium. Then, cell proliferation was determined using CCK-8 assay. *P < 0.05 compared with Ctrl group. (B) EC cells were treated with the TAMs-exo, negative mimic transfected TAMs-derived exosome, and miR-192-5p increased TAMs-derived exosomes. Then, CCK-8 was performed to detect the proliferation of EC cells. *P < 0.05 compared with Ctrl group. #P < 0.05 compared with TAMs-Exo group. (PNG 173 kb)

High Resolution (TIF 249 kb)

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Wang, Y., Ma, H., Li, Y. et al. MiR-192-5p-Modified Tumor-Associated Macrophages-Derived Exosome Suppressed Endometrial Cancer Progression Through Targeting IRAK1/NF-κB Signaling. Reprod. Sci. 29, 436–447 (2022). https://doi.org/10.1007/s43032-021-00789-8

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  • DOI: https://doi.org/10.1007/s43032-021-00789-8

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