α2,6-Sialylation promotes hepatocellular carcinoma cells migration and invasion via enhancement of nSmase2-mediated exosomal miRNA sorting.

Autor: Wang L; School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, 122406, China., Chen X; School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, 122406, China., Meng F; School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, 122406, China., Huang T; School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, 122406, China., Wang S; Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, China., Zheng Z; Department of Gastric Surgery, Cancer Hospital of China Medical University (Liaoning Cancer Hospital and Institute), Liaoning, China., Zheng G; Department of Gastric Surgery, Cancer Hospital of China Medical University (Liaoning Cancer Hospital and Institute), Liaoning, China., Li W; School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, 122406, China., Zhang J; School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, 122406, China. jnzhang@dlut.edu.cn., Liu Y; School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, 122406, China. liuyubo@dlut.edu.cn.
Jazyk: angličtina
Zdroj: Journal of physiology and biochemistry [J Physiol Biochem] 2023 Feb; Vol. 79 (1), pp. 19-34. Date of Electronic Publication: 2022 Aug 19.
DOI: 10.1007/s13105-022-00917-1
Abstrakt: Exosomes have a critical role in the intercellular communication and metastatic progression of hepatocellular carcinoma (HCC). Recently, our group showed that α2, 6-sialylation played an important role in the proliferation- and migration-promoting effects of cancer-derived exosomes. However, the molecular basis remains elusive. In this study, the mechanism of α2, 6-sialylation-mediated specific microRNAs (miRNA) sorting into exosomes was illustrated. We performed miRNA profiling analysis to compare exosomes from HCC cell lines that differ only in α2, 6-sialylation status. A total of 388 differentially distributed miRNAs were identified in wild-type and β-galactoside α2, 6-sialyltransferase I (ST6Gal-I) knockdown MHCC-97H cells-derived exosomes. Neutral sphingomyelinase-2 (nSmase2), an important regulator mediating the sorting of exosomal miRNAs, was found to be a target of ST6Gal-I. The reduction of α2, 6-sialylation could impair the activity of nSmase2, as well as the nSmase2-dependent exosomal miRNAs sorting. This α2,6-sialylation-dependent sorting exerted an augmentation of motility on recipient HCC cells. Our data further demonstrated that α2,6-sialylation-mediated sorting of exosomal miR-100-5p promoted the migration and invasion of recipient HepG2 cells via the PI3K/AKT signaling pathway. The cellular metastasis-related gene CLDN11 was confirmed as a direct target of exosomal miR-100-5p, which elevated the mobility of recipient HCC cells. In conclusion, our results showed that α2,6-sialylation modulates nSmase2-dependent exosomal miRNAs sorting and promotes HCC progression.
(© 2022. The Author(s) under exclusive licence to University of Navarra.)
Databáze: MEDLINE
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