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. 2022 May 25;12:884369. doi: 10.3389/fonc.2022.884369

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Copyright © 2022 Wang, Wang, Zhang, Shao, Luo, Wang and Han

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) and the copyright owner(s) 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.

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Hypoxia-induced microenvironment affects the regulation of HCC by EVs : The role of EVs derived from HCC on immune cells in the hypoxic environment. ① Suppressing the proliferation of T cells or rendering them incompetent. ② Whether the inhibitory effect on IFN-β production by NK cells and the process of inducing macrophage polarization are enhanced remains to be verified. The role of HCC-derived EVs facilitates EMT. ③ In the hypoxic environments, miR-1273f is upregulated in HCC-derived EVs, acting on LHX6 to activate Wnt/β-catenin to promote EMT. ④ In the normoxic environment, HCC-derived EVs contain N1D1, which may activate the ERK/MAPK pathway in recipient HCC cells to promote EMT. Regulation of angiogenesis by HCC-derived EVs. ⑤ In the hypoxic environments, miR-155 is upregulated in HCC-derived EVs and promotes angiogenesis. ⑥ In the normoxic environment, HCC-derived EVs are enriched in N1D1 and HSP1, which promote angiogenesis.