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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1489679
This article is part of the Research Topic Role of Extracellular Vesicles in Cancer: Implications in Immunotherapeutic Resistance View all articles

Activated hepatic stellate cell-derived small extracellular vesicles facilitate M2 macrophage polarization and hepatoma progression via miR-27a-3p

Provisionally accepted
Yufeng Sun Yufeng Sun Jiayi Han Jiayi Han Wenxuan Yin Wenxuan Yin Haichen Wang Haichen Wang Jing Li Jing Li Weiqi Liu Weiqi Liu Xingwang Kuai Xingwang Kuai Jiaying Lv Jiaying Lv Juling Ji Juling Ji *
  • Nantong University, Nantong, China

The final, formatted version of the article will be published soon.

    The progression of hepatoma is heavily influenced by the microenvironment. Tumor-associated macrophages (TAMs) are considered to play a critical role in the tumor microenvironment (TME) and increase the aggressiveness of hepatoma. The activation of hepatic stellate cells (HSCs) is involved in hepatoma progression, and accumulating evidence demonstrates a change in microRNA (miRNA) expression during HSC activation. Therefore, the potential roles of HSCs-related miRNAs in macrophage differentiation and hepatoma progression deserve to be explored. The present study aimed to investigate the effects of miRNAs carried by small extracellular vesicles (sEVs) released by activated HSCs on hepatoma progression. The results indicated that miR-27a-3p was significantly upregulated in cells and corresponding sEVs during the activation of primary rat HSCs and human HSC line-LX2 cells. Furthermore, miR-27a-3p contributed to the proliferation and migration of hepatoma cells and promoted M2 polarization of macrophage. HSC-sEVs overexpressing miR-27a-3p can directly facilitate tumor progression and modulate macrophage polarization, indirectly contributing to hepatoma progression. Finally, Sprouty2 (SPRY2) was verified to be the target gene of miR-27a-3p. In conclusion, activated HSC-derived sEVs with high levels of miR-27a-3p might induce M2 macrophage polarization and promote hepatoma progression, providing new insights into the mechanism of hepatoma progression.

    Keywords: hepatic stellate cell, hepatoma, miRNA-27a-3p, Tumor-associated macrophages, extracellular vesicles

    Received: 01 Sep 2024; Accepted: 03 Dec 2024.

    Copyright: © 2024 Sun, Han, Yin, Wang, Li, Liu, Kuai, Lv and Ji. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Juling Ji, Nantong University, Nantong, China

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