Abstract
Gambogic acid (GA) has been observed to effectively impede the progression of numerous types of cancers. In this study, we investigated the effects of miR-1275 and Secreted Protein Acidic and Cysteine Rich (SPARC) on GA in gastric cancer (GC). miR-1275 and SPARC expression were determined in GC cell lines and tissues using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The correlation between miR-1275 and SPARC expression was ascertained using Pearson’s correlation coefficient. Cell proliferation was assessed using the cell counting kit-8 (CCK-8) assay. The Transwell assay was conducted to examine cell migration. A dual-luciferase reporter assay was used to verify the regulatory relationship between miR-1275 and SPARC. The levels of SPARC, Bcl-2, and Bax proteins were estimated using western blotting. To verify the effects of GA on the growth of GC cells in vivo, a tumorigenesis experiment was performed in nude mice. GA suppressed GC cell viability and migration, facilitated apoptosis, and inhibited tumor growth in vivo and in vitro. Low levels of miR-1275 been observed in GC cell lines and tissues. GA-treated GC cells manifested high miR-1275 levels. In functional experiments, miR-1275 enhanced the influence of GA on cell apoptosis, migration, and proliferation. Furthermore, GA treatment suppressed SPARC upregulation in GC cell lines and tissues. Pearson’s correlation coefficient revealed that miR-1275 expression negatively correlated with SPARC expression. Mechanistically, miR-1275 promoted growth inhibition in GA-treated GC cells by targeting SPARC. Our study indicates that miR-1275 enhances the suppressive effect of GA on GC progression by inhibiting SPARC expression. Through this study, we contribute to the knowledge of a new mechanism by which GA suppresses GC progression.
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The datasets that have been used and/or analyzed during the study are available from the corresponding author upon reasonable request.
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AC and PFX executed the experiments and analysis of data. XKZ and YH designed and devised the study. AC and JL obtained the data. PFX and JL processed and interpreted the data. This manuscript has been read and approved by all authors.
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This research has been approved by the Ethics Committee of Wuhan Hospital of Traditional Chinese Medicine (approval number: 2022013, Wuhan, China). The processing of clinical samples is in strict compliance with the ethical standards of the Declaration of Helsinki. All patients provided their written informed consent. The procedures executed in the animal study were approved by the animal ethics committee of Wuhan Hospital of Traditional Chinese Medicine (approval number: WHTCM2021174). All animal experiments comply with the ARRIVE guidelines.
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Cai, A., Xia, P., Zhou, X. et al. MiR-1275 Targeting SPARC Promotes Gambogic Acid-Induced Inhibition of Gastric Cancer. Biochem Genet 61, 2481–2495 (2023). https://doi.org/10.1007/s10528-023-10381-1
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DOI: https://doi.org/10.1007/s10528-023-10381-1