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

细胞外囊泡衍生的 LINC00511 通过 microRNA-193a-3p 依赖性调控纤溶酶原激活剂尿激酶,促进巨噬细胞极化,促进胰腺癌的糖酵解和线粒体氧化磷酸化

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作者:Tingting Zhang, Hongyang Yu, Yuxian Bai, Jiaming Song, Jiexin Chen, Yingjie Li, Yue Cui

Conclusion

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

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.

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.

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.

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