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Small extracellular vesicles containing miR-30a-3p attenuate the migration and invasion of hepatocellular carcinoma by targeting SNAP23 gene

Oncogene volume 40, pages 233–245 (2021)Cite this article

Abstract

Cancer cells under hypoxic, endoplasmic reticulum, and reactive oxygen species stress secrete copious amounts of small extracellular vesicles (sEVs) to promote tumor metastasis. The effects of blocking stress-induced sEV release on tumor metastasis remain unknown. We found that miR-30a-3p was selectively sorted into sEVs by hepatocellular carcinoma (HCC) cells under the influence of multiple stressors. miR-30a-3p removal from cancer cells through sEVs promoted HCC cell migration and invasion, whereas exogenous overexpression of miR-30a-3p could inhibit migration, invasion, and sEV release by directly targeting SNAP23. HCC cells efficiently absorbed hepatic stellate cell (HSC) sEVs, providing an advantage in the treatment of HCC using HSC sEVs. Treatment with HSC sEVs rich in miR-30a-3p cargo effectively attenuated HCC migration, invasion, and metastasis. Overall, sEVs containing miR-30a-3p decreased sEV secretion as well as the migration, invasion, and metastasis of HCC by directly targeting SNAP23, thereby providing an effective strategy to attenuate metastasis of HCC.

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Fig. 1: miR-30a-3p is downregulated under Hypoxia, ERS and ROS.
Fig. 2: miR-30a-3p is selectively sorted into sEVs.
Fig. 3: Low expression of miR-30a-3p promotes migration, invasion, and sEV release.
Fig. 4: miR-30a-3p regulates migration, invasion, and sEV release via targeting SNAP23.
Fig. 5: Treatment with LX-2-derived miR-30a-3p-containing sEVs suppresses migration and invasion.
Fig. 6: sEVs loaded with miR-30a-3p cargo alleviate migration and invasion of HCC in vitro.
Fig. 7: sEVs loaded with miR-30a-3p cargo alleviate migration and invasion of HCC in vivo.

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Acknowledgements

This work was supported by the National Nature Science Foundation of China [grant numbers 81773008, 81672756, 81872399, 81972897], the Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2015), the Natural Science Foundation of Guangdong Province [grant number 2017A030311023], the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program: 2017BT01S131 and the Guangzhou Technology Project [grant number 201804010044].

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  1. These authors contributed equally: Chengdong Liu, Xiaohan Zhou, Qian Long

Authors and Affiliations

  1. Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, PR China

    Chengdong Liu, Qian Long, Hanyi Zeng, Qingcan Sun & Li Liu

  2. Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, PR China

    Xiaohan Zhou, Yuting Chen & Dehua Wu

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Liu, C., Zhou, X., Long, Q. et al. Small extracellular vesicles containing miR-30a-3p attenuate the migration and invasion of hepatocellular carcinoma by targeting SNAP23 gene. Oncogene 40, 233–245 (2021). https://doi.org/10.1038/s41388-020-01521-7

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