NRSN2 promotes the malignant behavior of HPV-transfected laryngeal carcinoma cells through AMPK/ULK1 pathway mediated autophagy activation

Cancer Biol Ther. 2024 Dec 31;25(1):2334463. doi: 10.1080/15384047.2024.2334463. Epub 2024 Apr 3.

Abstract

Neurensin-2 (NRSN2) performs a pro-carcinogenic function in multiple cancers. However, the function of NRSN2 in HPV-infected laryngeal carcinoma (LC) remains unclear. HPV transfection was performed in LC cells. The mRNA and protein levels were monitored using RT-qPCR, immunoblotting, and IF. Cell viability and proliferation were found using the CCK-8 assay and Edu staining. Cell invasion, migration, and apoptosis were probed using the Transwell, wound healing, and flow cytometry, respectively. The autophagosome was observed using TEM. NRSN2 was overexpressed in HPV-transfected LC cells. Inhibition of NRSN2 restrained the autophagy and malignant behavior of HPV-transfected LC cells. Meanwhile, the inhibition of AMPK/ULK1 pathway limited the increased autophagy of HPV-transfected LC cells caused by NRSN2 overexpression. Furthermore, NRSN2 knockdown inhibits autophagy by suppressing AMPK/ULK1 pathway, thereby restraining the malignant behavior of HPV-transfected LC cells. Our research confirmed that HPV transfection increased the autophagy and malignant behavior of LC cells by regulating the NRSN2-mediated activation of the AMPK/ULK1 pathway, offering a new target for cure of LC.

Keywords: AMPK/ULK1 pathway; HPV; Laryngeal carcinoma; NRSN2; autophagy.

MeSH terms

  • AMP-Activated Protein Kinases
  • Autophagy / genetics
  • Autophagy-Related Protein-1 Homolog / genetics
  • Autophagy-Related Protein-1 Homolog / metabolism
  • Carcinoma*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Papillomavirus Infections*

Substances

  • AMP-Activated Protein Kinases
  • Autophagy-Related Protein-1 Homolog
  • ULK1 protein, human
  • Intracellular Signaling Peptides and Proteins

Grants and funding

This work is supported by Ningxia Hui Autonomous Region key research and development project (No. 2022BEG03103).