Publication:
CircAKT3 promotes cell proliferation, survival and glutamine metabolism of gastric cancer by activating SLC1A5 expression via targeting miR-515-5p

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Li-37-227-241-2022.pdf(14.39 MB)
Date
2022
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Authors
Li, Fei ; Zhang, Lixiao ; Sun, Qi
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Publisher
Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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DOI
https://doi.org/10.14670/HH-18-401
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info:eu-repo/semantics/article
Description
Abstract
Background. Gastric cancer (GC) is a common disorder in the population. Numerous studies have reported that the pathogenesis of GC is implicated in the dysregulation of circular RNAs (circRNAs). The aim of this study was to investigate the role and functional mechanism of circ_0000199 (circAKT3) in GC. Methods. The expression of circAKT3, miR-515-5p and solute carrier family 1 member 5 (SLC1A5) mRNA was measured by quantitative real-time PCR (qPCR). Cell proliferation was assessed by cell counting kit-8 (CCK-8) assay, colony formation assay and 5-ethynyl-2'- deoxyuridine (EdU) assay. Cell apoptosis was determined by flow cytometry assay and caspase 3/7 activity. The protein levels of glutaminase (GLS), proliferating cell nuclear antigen (PCNA) and cleavedcaspase3 were detected by western blot. The binding relationship between miR-515-5p and circAKT3 or SLC1A5 was verified by dual-luciferase reporter assay or RIP assay. The role of circAKT3 in vivo was investigated by establishing animal models. The abundance of Ki-67 and PCNA was detected by IHC assay. Results. The expression of circAKT3 in GC tissues and cells was enhanced. The knockdown of circAKT3 inhibited GC cell proliferation, survival and glutamine metabolism, as well as tumor growth in animal models. MiR-515-5p was a target of circAKT3, and miR-515-5p suppressed the expression of SLC1A5 by binding to SLC1A5 3'UTR. CircAKT3 relieved the inhibition of miR-515-5p on SLC1A5 expression by targeting miR515-5p. The effects of circAKT3 knockdown were reversed by miR-515-5p depletion, and the effects of miR-515-5p restoration were abolished by SLC1A5 overexpression. Conclusion. CircAKT3 promotes the malignant development of GC by activating SLC1A5 expression via targeting miR-515-5p.
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circAKT3 , Gastric cancer , miR-515-5p , SLC1A5
Citation
Histology and Histopathology Vol. 37, nº3 (2022)
URI
http://hdl.handle.net/10201/128425
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Histology and histopathology Vol.37, nº3 (2022)
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