Abstract
Objective
Cisplatin (DDP)-based chemotherapy is commonly referred to as advanced gastric cancer (GC). The purpose of this study was to unravel whether Linc00852 from DDP-resistant tumor cell-derived exosomes (Exos) promotes DDP resistance of GC cells.
Methods
Reverse transcription quantitative polymerase chain reaction was used to detect the expression of Linc00852, miR-514a-5p, COMM domain protein 7 (COMMD7) mRNA, Bax mRNA, and Bcl-2 mRNA. Western blot was used to measure the expression of COMMD7 protein. The IC50 value of DDP is determined by MTT assay. The cell proliferation ability was measured by colony formation test. The apoptosis ability was measured by flow cytometry. The interaction between Linc00852, miR-514a-5p, and COMMD7 was confirmed by luciferase reporter gene assay and RNA pull-down assay. Xenograft tumor model was used to study the effect of Linc00852 on DDP resistance in vivo.
Results
Linc00852 was up-regulated in DDP-resistant GC cells and their secreted exosomes. Down-regulating Linc00852 facilitated the sensitivity of DDP-resistant GC cells to DDP. Linc00852 bound to miR-514a-5p and COMMD7 was a target of miR-514a-5p. Linc00852 could regulate COMMD7 expression via targeting miR-514a-5p. Exosomes from DDP-resistant GC cells enhanced the resistance of recipient GC cells to DDP via exosomal delivery of Linc00852. Depletion of Linc00852 repressed the growth and DDP resistance of GC cells in vivo.
Conclusion
Linc00852 from DDP-resistant tumor cell-derived Exos regulates COMMD7 to promote drug resistance of GC cells through miR-514a-5p.
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Funding
The Natural Science Foundation program of Zhejiang Province Y18H030042.
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HW contributed to study design; SC and BF contributed to manuscript editing; JC contributed to experimental studies; DZ and CW contributed to data analysis. All authors read and approved the final manuscript.
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Shuguang Cao and Beilei Fu are co-first authors.
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10565_2021_9685_MOESM1_ESM.jpg
Supplementary Figure 1. Linc00852 loaded by GC cells-derived exosomes acts as a ceRNA of miR-514a-5p to promote COMMD7 expression and enhance DDP resistance of GC cells. (JPG 771 KB)
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Cao, S., Fu, B., Cai, J. et al. Linc00852 from cisplatin-resistant gastric cancer cell-derived exosomes regulates COMMD7 to promote cisplatin resistance of recipient cells through microRNA-514a-5p. Cell Biol Toxicol 39, 483–496 (2023). https://doi.org/10.1007/s10565-021-09685-y
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DOI: https://doi.org/10.1007/s10565-021-09685-y