USP18 Confers Paclitaxel Resistance in Non‐Small Cell Lung Cancer by Stabilizing SHANK1 Expression Via Deubiquitination
Year: 2025
Type: article
Abstract: Ubiquitin-specific protease 18 (USP18) has been identified to promote lung cancer growth and metastasis by deubiquitinating protein substrates. Herein, the action and mechanism of USP18 on paclitaxel resistance in non-small cell lung cancer (NSCLC) were investigated in this study. The mRNA and protein levels of USP18 and SH3 and multiple ankyrin repeat domains protein 1 (SHANK1) were detected by qRT-PCR and western blot analysis analyses. PTX resistance in NSCLC cells was determined by analyzing cell proliferation, apoptosis, and IC50 values using colony formation assay, flow cytometry, and CCK-8 assay, respectively. The glycolysis was determined by detecting glucose consumption, lactate production and ATP levels. Protein interaction was validated using Co-IP assay. Cellular ubiquitination analyzed the deubiquitination effect of USP18 on SHANK1. Animal experiments was performed for in vivo analysis. USP18 was highly expressed in PTX-resistant NSCLC tissues and cells. Silencing of USP18 promoted PTX sensitivity by suppressing the proliferation and glycolysis and inducing apoptosis in PTX-resistant NSCLC cells. Mechanically, USP18 deubiquitinated SHANK1 and stabilized its expression. SHANK1 was highly expressed in PTX-resistant NSCLC tissues and cells, and the deficiency of SHANK1 promoted the sensitivity of PTX-resistant NSCLC cells to PTX. Moreover, the enhanced sensitivity of PTX-resistant NSCLC cells to PTX that was caused by USP18 silencing could be reversed by SHANK1 overexpression. In addition, USP18 silencing reinforced PTX-induced growth inhibition in NSCLC by regulating SHANK1. In conclusion, USP18 conferred paclitaxel resistance in NSCLC by stabilizing SHANK1 expression via deubiquitination.
DOI: 10.1002/jbt.70197
Authors: Lixun Chai, Yanlong Sun, Yunfei Wang, Chenhui Zhao
Institutions: Shanxi Medical University, Shanxi Academy of Medical Sciences
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4408540221