Extracellular vesicle-derived LINC00511 promotes glycolysis and mitochondrial oxidative phosphorylation of pancreatic cancer through macrophage polarization by microRNA-193a-3p-dependent regulation of plasminogen activator urokinase

Abstract

Objective

The involvement of tumor-derived extracellular vesicles (EVs) in macrophage polarization has been reported. In our present study, we tried to discuss the regulatory role of LINC00511 encapsulated in pancreatic cancer (PCa) cell-derived EVs in the development and progression of PCa.

Methods

EVs from PCa cell line BxPC-3 culture medium were collected and subsequently identified by electron microscopy and nanoparticle tracking analysis. The expression pattern of LINC00511 in PCa cell-derived EVs was determined. The interaction among LINC00511, microRNA-193a-3p, and plasminogen activator urokinase (PLAU) was explored. After co-culture of PCa cell-derived EVs with macrophages, the regulatory roles of LINC00511 in macrophage polarization, PCa cell functions, glucose consumption, lactate production, glycolysis, and mitochondrial oxidative phosphorylation were investigated.

Results

PCa cell line BxPC-3 had highly expressed LINC00511 and LINC00511 could be internalized by macrophages. LINC00511 affected macrophage polarization through miR-193a-3p-dependent regulation of PLAU expression. Besides, EV-derived LINC00511 accelerated glycolysis and promoted mitochondrial oxidative phosphorylation of PCa cells through macrophage polarization, thus inducing invasion and migration of PCa cells.

Conclusion

LINC00511 encapsulated in PCa cell-derived EVs facilitates glycolysis of PCa cells through regulation of macrophage polarization in the tumor microenvironment.

Keywords:

• LINC00511
• pancreatic cancer
• extracellular vesicles
• tumor microenvironment
• microRNA-193a-3p
• glycolysis

Ethics approval

This article does not contain any studies with human or animal subjects performed by the any of the authors.

Author contributions

TZ contributed to the study concepts, study design; JS, JC, YL, YC contributed to the experimental studies and data acquisition; HY, YB contributed to the data analysis and statistical analysis; TZ contributed to the manuscript preparation, manuscript editing and review; All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.

Additional information

Funding

This study was supported by Beijing Medical Award Fund [No. YXJL-2020-0785-0974].