Circ_0008315 promotes tumorigenesis and cisplatin resistance and acts as a nanotherapeutic target in gastric cancer

Circ_0008315 promotes tumorigenesis and cisplatin resistance and acts as a nanotherapeutic target in gastric cancer

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Abstract Introduction Cisplatin-based chemotherapy is one of the fundamental therapeutic modalities for gastric cancer (GC).Chemoresistance to cisplatin is a great clinical challenge, and its underlying mechanisms remain poorly understood.Circular RNAs (circRNAs) are involved in sukin body lotion woolworths the pathophysiology of multiple human malignancies.Methods High-throughput sequencing was performed to determine the differentially expressed profile of circRNA in GC tissues and cisplatin-resistant GC cells.

Quantitative real-time polymerase chain reaction and Fluorescence in situ hybridization was utilized to confirm the dysregulation of circ_0008315 in GC tissues.To evaluate the prognostic significance of circ_0008315 in GC, we used Kaplan-Meier plot.The self-renewal ability of drug-resistant GC cell was verified through tumor sphere formation assay.GC organoids were constructed to simulate the tumor microenvironment and verified the function of circ_0008315 in cisplatin resistance of gastric cancer.

In vivo evaluation was conducted using patient-derived xenograft models.Dual-luciferase reporter gene, RNA immunoprecipitation and miRNA pull-down assays were employed to investigate the molecular mechanisms of circ_0008315 in GC.Results We revealed that a novel circRNA hsa_circ_0008315 was upregulated in GC and cisplatin-resistant GC cells.Elevated circ_0008315 was also observed in cisplatin-resistant GC organoid model.

High circ_0008315 expression predicted unfavorable survival outcome in GC patients.Downregulation of circ_0008315 expression inhibited proliferation, mobility, and epithelial-mesenchymal transition of GC cells in vitro and in vivo.Reducing circ_0008315 expression in cisplatin-resistant GC organoid model reversed simply southern cat shirt cisplatin resistance.Mechanistically, circ_0008315 modulated the stem cell properties of GC through the miR-3666/CPEB4 signaling pathway, thereby promoting cisplatin resistance and GC malignant progression.

Furthermore, we developed PLGA-PEG nanoparticles targeting circ_0008315, and the nanoparticles could effectively inhibit GC proliferation and cisplatin resistance.Conclusion Circ_0008315 exacerbates GC progression and cisplatin resistance, and can be used as a prognostic predictor.Circ_0008315 may function as a promising nanotherapeutic target for GC treatment.Graphical Abstract.