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

作者：Chengdong Liu, Xiaohan Zhou, Long Qian, Hanyi Zeng, Qingcan Sun, Yuting Chen, Dehua Wu, Li Liu · 发表于：Oncogene · 年份：2020 · DOI：10.1038/s41388-020-01521-7 · 被引用次数：44 · 研究领域：Extracellular vesicles in disease、MicroRNA in disease regulation、Circular RNAs in diseases

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.