Hepatocellular carcinoma cells-derived exosomal microRNA-378b enhances hepatocellular carcinoma angiogenesis.

Abstract

OBJECTIVE:

It has been already accepted that hepatocellular carcinoma (HCC) cells-derived exosomes mediate HCC development partially through transferring microRNAs (miRNAs). Illuminated by that, this work pivoting on HCC specifically starts from miR-378b in HepG2 cells-derived exosomes, involving with transforming growth factor β receptor III (TGFBR3).

METHODS:

HCC tissue and normal tissue specimens were resected, in which miR-378b and TGFBR3 expression were tested. The connection between miR-378b and TGFBR3 was assessed. HepG2 cells were transfected with miR-378b and TGFBR3-related sequences to explore their functions in HCC cell progression. The extracted exosomes from HepG2 cells were identified and co-cultured with human umbilical vein endothelial cells to explore their roles in HCC cell progression and angiogenesis. Tumorigenesis in mice was conducted for further validation of the findings in cells.

RESULTS:

Up-regulated miR-378b and down-regulated TGFBR3 presented in HCC, and miR-378b targeted TGFBR3. Depleted miR-378b disturbed HCC cell migration and promoted apoptosis. Knockdown of TGFBR3 reversed the effects of down-regulated miR-378b on HCC cells. HepG2 cells-derived exosomes promoted angiogenesis in vitro and tumor growth in vivVo, which would be further enhanced by miR-378b overexpression while impaired by miR-378b down-regulation.

CONCLUSION:

It is elucidated that HepG2 cells-derived exosomal miR-378b enhances HCC cell progression and angiogenesis, which may be linked with TGFBR3, providing therapeutic agents for HCC curing.

• Authors: Wei Chen, Li Huang, Junhua Liang, Yingjian Ye, Shan He, Junli Niu
• Journal: Life sciences (Life Sci) Vol. 273 Pg. 119184 (May 15 2021) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 33577844 (Publication Type: Journal Article, Retracted Publication)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers, Tumor
• MIRN378 microRNA, human
• MicroRNAs

Topics

• Adult
• Aged
• Animals
• Apoptosis
• Biomarkers, Tumor (genetics)
• Carcinoma, Hepatocellular (blood supply, genetics, pathology)
• Cell Proliferation
• Exosomes (genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Liver Neoplasms (blood supply, genetics, pathology)
• Male
• Mice
• Mice, Nude
• MicroRNAs (genetics)
• Middle Aged
• Neovascularization, Pathologic (pathology)
• Prognosis
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays