ExosomallncRNA UCA1from cancer-associated fibroblasts enhances chemoresistance in vulvar squamous cell carcinoma cells

Aim In the current work, we aimed to explore whether Cancer-associated fibroblasts (CAF) exosomes played crucial roles in vulvar squamous cell carcinoma (VSCC) chemoresistance via mediating long noncoding RNAs (lncRNA). Methods The IC50 value and cell apoptosis were assessed by the Cell Counting-8 Kit (CCK-8) assay and flow cytometry, respectively. Western blot analysis was used for the measurement of protein levels. The levels of urothelial cancer-associated 1 (UCA1), miR-103a and WEE1 G2 checkpoint kinase (WEE1) mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The target relationships among miR-103a, UCA1 and WEE1 were confirmed by dual-luciferase reporter assays. Xenograft model mice were established to observe the impact of exosomal UCA1 on cisplatin (CDDP) resistancein vivo. Results Our data indicated that CAF enhanced CDDP resistance of VSCC cellsin vitro. Extracellular UCA1 was transferred by exosomes derived from CAF. Exosomal UCA1 derived from CAF conferred VSCC cell resistance to CDDP. Moreover, UCA1 functioned as a miR-103a sponge in VSCC cells. The promotion of exosomal UCA1 on VSCC cell resistance to CDDP was mediated by miR-103a. WEE1 was a direct target of miR-103a, and exosomal miR-103a from CAF weakened CDDP resistance of VSCC cells by WEE1. Furthermore, exosomal UCA1 regulated WEE1 expression through sponging miR-103a. Additionally, exosomal UCA1 enhanced tumor growth and CDDP resistancein vivo. Conclusion Our findings suggested exosomal UCA1 derived from CAF conferred VSCC cell resistance to CDDPin vitroandin vivoat least partly through the miR-103a/WEE1 axis, highlighting a novel therapeutic method for improving the clinical benefits of CDDP chemotherapy in VSCC patients.

Automated summary

Our study demonstrated that CAF-derived exosomal UCA1 contributes to chemoresistance in VSCC cells both in vitro and in vivo, partly mediated by the miR-103a/WEE1 axis. This suggests a potential therapeutic approach to enhance the efficacy of CDDP chemotherapy in VSCC patients.