Tumor cells derived-extracellular vesicles transfer miR-3129 to promote hepatocellular carcinoma metastasis by targeting TXNIP

  • Dig Liver Dis. 2021 Apr;53(4):474-485. doi: 10.1016/j.dld.2021.01.003.
Yang Yang  1 ,  Feifei Mao  2 ,  Lei Guo  1 ,  Jie Shi  1 ,  Mengchao Wu  1 ,  Shuqun Cheng  1 ,  Weixing Guo  3
Affiliations
  • 1. Department of Hepatic Surgery VI, Third Affiliated Hospital of Second Military Medical University, Shanghai, 200438, China.
  • 2. Department of Hepatic Surgery VI, Third Affiliated Hospital of Second Military Medical University, Shanghai, 200438, China; Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
  • 3. Department of Hepatic Surgery VI, Third Affiliated Hospital of Second Military Medical University, Shanghai, 200438, China. Electronic address: [email protected].
PMID: 33563583 DOI: 10.1016/j.dld.2021.01.003
Abstract

Background: Hepatocellular carcinoma (HCC) is the most predominant primary liver Cancer. Extracellular vesicles (EV)-mediated MicroRNA (miRNA) delivery is critical in Cancer metastasis. We aimed to identify the mechanism of HCC cell-derived EVs-mediated miR-3129 in HCC.

Methods: After EVs isolation and identification, miR-3129 expression in plasma EVs was evaluated and its diagnostic efficiency was analyzed. miR-3129 inhibitor was transfected into HepG2 and SMMC7721 cells, and cell malignant episodes were assessed. HCC cells were incubated with EVs from MHCC-97H cells and transfected with miR-3129 inhibitor and/or TXNIP. The nude mice were injected with MHCC-97H cells-EV or MHCC-97H cells-EV/miR-3129 inhibitor, and HCC growth and metastasis were assessed.

Results: miR-3129 was highly expressed in plasma EVs from HCC patients, which was the essential diagnostic biomarker for HCC. miR-3129 downregulation inhibited the malignant episodes of HCC cells. MHCC-97H cell-EVs were absorbed by HCC cells and transferred miR-3129 to HCC cells. EVs-carried miR-3129 promoted malignant episodes of HCC cells, which were weakened by miR-3129 inhibition in EVs. miR-3129 targeted TXNIP. TXNIP overexpression averted the effect of EVs-carried miR-3129 in HCC. In vivo, MHCC-97H cell-EVs transferred miR-3129 to facilitate HCC growth and metastasis.

Conclusion: MHCC-97H cell-EVs transferred miR-3129 to promote HCC metastasis by targeting TXNIP.

Keywords
Epithelial-mesenchymal-transition; Extracellular vesicles; Hepatocellular carcinoma; Metastasis; TXNIP; microRNA-3129.
Products