Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 599, Issue -, Pages 120-126Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2022.02.048
Keywords
Triple negative breast cancer; Ubiquitin speci fic peptidase 18; Paclitaxol resistance; Autophagy
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Funding
- National Key Research and Development Program of China [2017YFA0505602]
- Na-tional Natural Science Foundation [81872246, 81930078, 81802756]
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USP18 expression is increased in paclitaxol-resistant TNBC cells. Overexpression of USP18 reduces paclitaxol sensitivity and induces autophagy, leading to chemotherapy resistance.
Paclitaxol is a first-line treatment for triple-negative breast cancer (TNBC). The molecular mechanisms underlying paclitaxol resistance in TNBC remain largely unclear. In this study, differential expressed genes (DEGs) between TNBC cells and paclitaxol-resistant (taxol-R) TNBC cells were screened by bioinformatics analysis. Among these DEGs, USP18 mRNA expression was significantly increased in taxol-R TNBC cells. USP18 overexpression reduced paclitaxol sensitivity by decreasing paclitaxol-induced apoptosis and cell cycle arrest in TNBC cells. In contrast, USP18 knockdown increased paclitaxol mediated anticancer activity in taxol-R TNBC cells in vitro and in vivo. Mechanistically, USP18 induced autophagy, an important pathway in chemotherapy resistance. The autophagy inhibitor leupeptin could effectively reverse the effect of USP18 on paclitaxol resistance phenotype. These findings suggested that USP18 may be a promising target for overcoming paclitaxol resistance in TNBC. (c) 2022 Elsevier Inc. All rights reserved.
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