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Related Experiment Video

Updated: May 21, 2025

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USP18 Confers Paclitaxel Resistance in Non-Small Cell Lung Cancer by Stabilizing SHANK1 Expression Via

Lixun Chai1, Yanlong Sun1, Yunfei Wang1

  • 1Department of Thoracic surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, Shanxi, China.

Journal of Biochemical and Molecular Toxicology
|March 17, 2025
PubMed
Summary

Ubiquitin-specific protease 18 (USP18) promotes paclitaxel resistance in non-small cell lung cancer (NSCLC) by stabilizing SHANK1. USP18 deubiquitinates SHANK1, enhancing its expression and conferring resistance. Silencing USP18 restores sensitivity to paclitaxel in NSCLC.

Keywords:
PTXSHANK1USP18deubiquitinationglycolysispaclitaxel resistance

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Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality.
  • Paclitaxel (PTX) is a key chemotherapeutic agent for NSCLC, but resistance remains a significant challenge.
  • Ubiquitin-specific protease 18 (USP18) is implicated in cancer progression, but its role in PTX resistance is unclear.

Purpose of the Study:

  • To investigate the role and mechanism of USP18 in paclitaxel resistance in NSCLC.
  • To elucidate the relationship between USP18, SHANK1, and PTX sensitivity in NSCLC cells.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) and Western blot to assess USP18 and SHANK1 expression.
  • Cell proliferation, apoptosis, and IC50 assays (colony formation, flow cytometry, CCK-8) to determine PTX resistance.
  • Glycolysis assays (glucose consumption, lactate production, ATP levels) and Co-immunoprecipitation (Co-IP) to validate protein interactions and deubiquitination.
  • In vivo animal experiments for further validation.

Main Results:

  • USP18 was significantly upregulated in PTX-resistant NSCLC tissues and cells.
  • USP18 silencing suppressed proliferation and glycolysis, induced apoptosis, and enhanced PTX sensitivity in resistant NSCLC cells.
  • USP18 deubiquitinates and stabilizes SHANK1, which is also highly expressed in PTX-resistant cells.
  • SHANK1 deficiency increased PTX sensitivity, and SHANK1 overexpression reversed the effects of USP18 silencing.
  • USP18 silencing enhanced PTX-induced growth inhibition by regulating SHANK1.

Conclusions:

  • USP18 confers paclitaxel resistance in NSCLC by stabilizing SHANK1 expression through deubiquitination.
  • USP18 and SHANK1 represent potential therapeutic targets for overcoming PTX resistance in NSCLC.