Circ_0057553/miR-515-5p Regulates Prostate Cancer Cell Proliferation, Apoptosis, Migration, Invasion and Aerobic Glycolysis by Targeting YES1.

ONCOTARGETS AND THERAPY(2020)

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摘要
Background: Prostate cancer (PCa) is one of the most common malignant cancer in males worldwide. Circular RNAs (CircRNAs) are novel type of non-coding RNAs. Recently, circRNAs have been reported participating in various cancers, including prostate cancer. However, the function and mechanism of circ 0057553 remain to be elucidated. Methods and Materials: The RNA expression levels of circ_0057553, miR-515-5p, YES proto-oncogene 1 (YES1) and glycolytic genes mRNA were detected by qRT-PCR in PCa tissues or cells. Western blotting was performed to analyze YES1 protein level. Cell viability, migration and invasion and cell apoptosis were assessed by cell counting kit-8 (CCK-8) assay, transwell assay and flow cytometry. In addition, the effects of cell glycolysis were evaluated by measuring lactate production, glucose consumption and adenosine triphosphate (ATP) level. Moreover, dual-luciferase reporter assay was used to detect the target sites of circ_0057553 and miR-515-5p, miR-515-5p and YES1. RNA immunoprecipitation (RIP) was conducted to evaluate the target relationship between circ_0057553 and miR-515-5p. Xenograft mouse model was conducted to measure tumor formation in vivo. Results: Circ_0057553 was significantly up-regulated in PCa tissues and cells. Knockdown of circ_0057553 inhibited cell viability, migration, invasion and glycolysis and facilitated apoptosis in PCa cells. Furthermore, circ_0057553 bound to miR-515-5p and miR-515-5p directly targeted YES1. Interestingly, miR-515-5p inhibitor partially rescued the function of circ_0057553 knockdown, while YES1 restored the effects of miR-515-5p overexpression. Circ_0057553 down-regulation remarkably decreased tumor volume and weight in vivo. Conclusion: Circ_0057553 affected PCa cell viability, migration, invasion, apoptosis and glycolysis through miR-515-5p/YES1 axis.
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关键词
circ_0057553,miR-515-5p,YES1,prostate cancer
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