USP5 knockdown alleviates lung cancer progression via activating PARP1-mediated mTOR signaling pathway

Biol Direct. 2023 Apr 14;18(1):16. doi: 10.1186/s13062-023-00371-z.

Abstract

Background: With the rapidly increasing morbidity and mortality, lung cancer has been considered one of the serious malignant tumors, affecting millions of patients globally. Currently, the pathogenesis of lung cancer remains unclear, hindering the development of effective treatment. This study aims to investigate the mechanisms of lung cancer and develop an effective therapeutic approach for intervention in preventing lung cancer progress.

Methods: The USP5 levels are detected in lung cancerous and paracancerous tissue by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting methods to explore their roles in lung cancer progression. MTT, colony assay, and transwell chamber approaches are employed to measure cell viability, proliferation, and migration, respectively. Further, flow cytometry experiments are performed to examine the effect of USP5 on lung cancer. Finally, the investigations in vivo are executed using the mice subcutaneous tumor model to identify the effect of USP5 in promoting lung cancer development.

Results: Notably, USP5 is highly expressed in lung cancer, USP5 overexpression promoted the proliferation and migration in the lung cancer cell lines, H1299 and A549, while knockdown of USP5 inhibited these via regulating the PARP1-mediated mTOR signaling pathway. Furthermore, the subcutaneous tumors model was established in C57BL/6 mice, and the volume of subcutaneous tumors was significantly reduced after silencing USP5, while increased after USP5 overexpression and decreased significantly with shRARP1 treatment at the same time.

Conclusions: Together, USP5 could promote the progression of lung cancer cells by mTOR signaling pathway and interacting with PARP1, indicating that USP5 may become a new target for lung cancer treatment.

Keywords: Lung cancer; PARP1; USP5; mTOR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Lung / metabolism
  • Lung Neoplasms* / genetics
  • Mice
  • Mice, Inbred C57BL
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism
  • TOR Serine-Threonine Kinases / pharmacology
  • TOR Serine-Threonine Kinases / therapeutic use
  • Ubiquitin-Specific Proteases / metabolism
  • Ubiquitin-Specific Proteases / pharmacology

Substances

  • TOR Serine-Threonine Kinases
  • Ubiquitin-Specific Proteases
  • Usp5 protein, mouse
  • Parp1 protein, mouse