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LncRNA SH3PXD2A-AS1 facilitates cisplatin resistance in non-small cell lung cancer by regulating FOXM1 succinylation

Yunfeng Chen1, Siyan Wu1, Yu Han1

  • 1Department of Respiratory and Critical Care Medicine, The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, No. 269, University Road, Tongshan District, Xuzhou, Jiangsu, 221116, China.

BMC Cancer
|July 17, 2024
PubMed
Abstract

Insights

SH3PXD2A-AS1 promotes cisplatin resistance in non-small cell lung cancer (NSCLC) by affecting FOXM1 succinylation through SIRT7. Inhibiting SH3PXD2A-AS1 may offer a new therapeutic strategy for NSCLC patients.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Long noncoding RNAs (lncRNAs) are key regulators in non-small cell lung cancer (NSCLC).
  • Cisplatin (DDP) resistance diminishes the efficacy of chemotherapy in NSCLC patients.
  • SH3PXD2A-AS1 is investigated for its role in DDP resistance in NSCLC.

Purpose of the Study:

  • To investigate the effect of SH3PXD2A-AS1 on DDP resistance in NSCLC.
  • To elucidate the underlying molecular mechanisms involving FOXM1 succinylation and SIRT7.

Main Methods:

  • Cell counting kit-8 and flow cytometry for proliferation and apoptosis assays.
  • Co-immunoprecipitation, RNA pull-down, RIP, and FISH to assess molecular interactions.
  • Western blot and IP to analyze protein succinylation.
  • Xenografted tumor model in mice to evaluate in vivo effects.

Main Results:

  • SH3PXD2A-AS1 expression is elevated in DDP-resistant NSCLC cells.
  • Silencing SH3PXD2A-AS1 suppresses cell viability, promotes apoptosis, and decreases FOXM1 levels while increasing FOXM1 succinylation.
  • SIRT7 interacts with FOXM1, inhibiting its succinylation at K259; SIRT7 overexpression reverses the effects of SH3PXD2A-AS1 silencing.
  • SH3PXD2A-AS1 inhibition suppressed tumor growth and related protein markers in vivo.

Conclusions:

  • SH3PXD2A-AS1 promotes DDP resistance in NSCLC by regulating FOXM1 succinylation via SIRT7.
  • Targeting SH3PXD2A-AS1 presents a potential therapeutic strategy for NSCLC.
Keywords:
DDP resistanceFOXM1Non-small cell lung cancerSH3PXD2A-AS1SIRT7Succinylation

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