KEY TAKEAWAYS
- The study aimed to examine SH3PXD2A-AS1’s impact on DDP resistance in patients with NSCLC.
- SH3PXD2A-AS1 enhances DDP resistance in NSCLC cells via FOXM1/SIRT7, suggesting a promising therapeutic approach.
Long noncoding RNAs (lncRNAs) have crucial regulatory roles in non-small cell lung cancer (NSCLC). Cisplatin (DDP) resistance has significantly reduced the effectiveness of DDP-based chemotherapy in patients with NSCLC.
Yunfeng Chen and the team aimed to investigate how SH3PXD2A antisense RNA 1 (SH3PXD2A-AS1) affects DDP resistance in patients with NSCLC.
The study detected proliferation and apoptosis of DDP-resistant NSCLC cells using cell counting kit-8 and flow cytometry assays. The interaction between SH3PXD2A-AS1 and sirtuin 7 (SIRT7) was assessed through co-immunoprecipitation (Co-IP), RNA pull-down, RNA immunoprecipitation (RIP), RNA fluorescence in situ hybridization, and immunofluorescence assays.
Succinylation (SUCC) of Forkhead Box M1 (FOXM1) was analyzed by IP and Western blot assays. The role of SH3PXD2A-AS1 in patients was explored using a xenografted tumor model.
The results showed elevated expression of SH3PXD2A-AS1 in DDP-resistant NSCLC cells, with its knockdown leading to suppressed cell viability and increased apoptosis. Silencing SH3PXD2A-AS1 also reduced FOXM1 protein levels while increasing FOXM1-SUCC levels.
SIRT7 interacted with FOXM1, inhibiting FOXM1 SUCC at the K259 site in HEK-293T cells. Overexpressing SIRT7 reversed the increased FOXM1-SUCC protein levels and apoptosis, and the decreased cell viability caused by SH3PXD2A-AS1 silencing.
In tumor-bearing mice, inhibiting SH3PXD2A-AS1 suppressed tumor growth and reduced Ki67, SIRT7, and FOXM1 protein levels.
The study concluded that SH3PXD2A-AS1 promotes DDP resistance in NSCLC cells by regulating FOXM1 SUCC through SIRT7, suggesting a promising therapeutic approach for NSCLC.
This work was supported by Xuzhou Science and Technology Bureau Focuses on Research and Development Plan, Open Subject of Key Laboratory of Universities in Jiangsu Province,Scientific Research Project of Jiangsu Provincial Health Commission and Development Fund of The Affiliated Hospital of Xuzhou Medical University.
Source: https://pubmed.ncbi.nlm.nih.gov/39020302/
Chen Y, Wu S, Han Y, et al. (2024). “LncRNA SH3PXD2A-AS1 facilitates cisplatin resistance in non-small cell lung cancer by regulating FOXM1 succinylation.” BMC Cancer. 2024;24(1):848. Published 2024 Jul 17. doi:10.1186/s12885-024-12624-9
