Exosomes secreted by M2 macrophages promote cancer stemness of hepatocellular carcinoma via the miR-27a-3p/TXNIP pathways
Wenxiao Li, Xiaowen Xin, Xiujun Li, Jianli Geng, Yunfu Sun
Abstract
OBJECTIVE: Accumulating evidence has suggested that microRNAs (miRNAs) derived from M2 macrophage-derived exosomes (M2 exosomes) can regulate the progression of hepatocellular carcinoma (HCC). Nevertheless, the effect of miR-27a-3p derived from M2 exosomes on HCC has not been reported. We aim to explore the role of M2 exosomal miR-27a-3p in the cancer stemness of HCC via regulating thioredoxin-interacting protein (TXNIP). METHODS: Exosomes were extracted from transfected M2 macrophages and were then co-cultured with HCC cells. Expression of miR-27a-3p and TXNIP, stemness, proliferation, drug resistance, migration, invasion and in vivo tumorigenicity of HCC cells were determined to assess the role of M2 exosomal miR-27a-3p in HCC. The binding relationship between miR-27a-3p and TXNIP was detected. RESULTS: MiR-27a-3p was upregulated and TXNIP was downregulated in HCC cells, and M2 exosomes further upregulated miR-27a-3p. The upregulated M2 exosomal miR-27a-3p promoted stemness, proliferation, drug resistance, migration, invasion and in vivo tumorigenicity of HCC cells. TXNIP was confirmed as a target gene of miR-27a-3p. CONCLUSION: M2 macrophages-derived exosomal miR-27a-3p promotes cancer stemness of HCC via downregulating TXNIP.