Role of glutaminyl-peptide cyclotransferase in breast cancer doxorubicin sensitivity

Doxorubicin (DOX) is one of the most effective and widely used chemotherapeutic drugs. However, DOX resistance is a critical risk problem for breast cancer treatment. Previous studies have demonstrated that metadherin (MTDH) involves in DOX resistance in breast cancer, but the exact mechanism remain...

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Published in:Cancer biology & therapy 2024-12, Vol.25 (1), p.2321767-2321767
Main Authors: Xu, Bin, Yang, Liu, Yang, Lixian, Al-Maamari, Ahmed, Zhang, Jingyu, Song, Heng, Wang, Meiqi, Su, Suwen, Song, Zhenchuan
Format: Article
Language:English
Subjects:
Aminoacyltransferases
Breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Cell Line, Tumor
doxorubicin
Doxorubicin - pharmacology
Doxorubicin - therapeutic use
Female
Humans
Membrane Proteins - genetics
Membrane Proteins - metabolism
MTDH/NF-κB axis
NF-kappa B - metabolism
QPCT
Research Paper
RNA-Binding Proteins - genetics
sensitivity
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Summary:Doxorubicin (DOX) is one of the most effective and widely used chemotherapeutic drugs. However, DOX resistance is a critical risk problem for breast cancer treatment. Previous studies have demonstrated that metadherin (MTDH) involves in DOX resistance in breast cancer, but the exact mechanism remains unclear. In this study, we found that glutaminyl-peptide cyclotransferase (QPCT) was a MTDH DOX resistance-related downstream gene in breast cancer. Elevated expression of QPCT was found in the GEPIA database, breast cancer tissue, and breast cancer cells. Clinical data showed that QPCT expression was positively associated with poor prognosis in DOX-treated patients. Overexpression of QPCT could promote the proliferation, invasion and migration, and reduce DOX sensitivity in MCF-7 and MDA-MB-231 cells. Mechanistically, MTDH positively regulates the expressions of NF-κB (p65) and QPCT, and NF-κB (p65) directly regulates the expression of QPCT. Therefore, MTDH/NF-κB (p65)/QPCT signal axis was proposed. Collectively, our findings delineate the mechanism by which the MTDH/NF-κB (p65) axis regulate QPCT signaling and suggest that this complex may play an essential role in breast cancer progression and affect DOX sensitivity.
ISSN:1538-4047
1555-8576
DOI:10.1080/15384047.2024.2321767