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SJB2-043, a USP1 Inhibitor, Suppresses A549 Cell Proliferation, Migration, and EMT via Modulation of PI3K/AKT/mTOR,

Lipeng Wu1, Meng Yu1, Huosheng Liang2

  • 1Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University, Guangzhou 510645, China.

Current Issues in Molecular Biology
|March 26, 2025
PubMed
Abstract

Insights

The USP1 inhibitor SJB2-043 suppresses non-small cell lung cancer (NSCLC) cell growth and migration. This compound enhances apoptosis and impacts the cell cycle, offering a potential new therapeutic strategy for NSCLC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality.
  • USP1 is implicated in cancer progression and serves as a potential therapeutic target.

Purpose of the Study:

  • To investigate the effects of the USP1 inhibitor SJB2-043 on A549 NSCLC cells.
  • To elucidate the underlying molecular mechanisms of SJB2-043's anti-cancer activity.

Main Methods:

  • Analysis of USP1 expression in NSCLC using public databases.
  • RNA sequencing and pathway enrichment analysis (KEGG, GO).
  • In vitro studies on A549 cells assessing proliferation, migration, apoptosis, and cell cycle via CCK-8, colony formation, wound healing, flow cytometry, and Western blotting.

Main Results:

  • USP1 overexpression correlates with poor prognosis in NSCLC.
  • SJB2-043 significantly inhibited A549 cell proliferation, migration, and colony formation, while inducing apoptosis.
  • SJB2-043 treatment led to G2 cell cycle arrest and modulated key proteins involved in cell cycle, apoptosis, EMT, and signaling pathways (MAPK, Wnt/β-catenin, PI3K/AKT/mTOR).

Conclusions:

  • SJB2-043 effectively suppresses NSCLC cell proliferation, migration, and epithelial-mesenchymal transition.
  • The observed effects are mediated by the inhibition of MAPK, Wnt/β-catenin, and PI3K/AKT/mTOR signaling pathways.
  • SJB2-043 demonstrates potential as an anti-NSCLC therapeutic agent.
Keywords:
SJB2-043USP1 inhibitorepithelial–mesenchymal transition (EMT)non-small cell lung cancer (NSCLC)

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