Role of glutaminyl-peptide cyclotransferase in breast cancer doxorubicin sensitivity
ABSTRACTDoxorubicin (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 mechanis...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2024-12-01
|
| Series: | Cancer Biology & Therapy |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/15384047.2024.2321767 |
| _version_ | 1797193783653171200 |
|---|---|
| author | Bin Xu Liu Yang Lixian Yang Ahmed Al-Maamari Jingyu Zhang Heng Song Meiqi Wang Suwen Su Zhenchuan Song |
| author_facet | Bin Xu Liu Yang Lixian Yang Ahmed Al-Maamari Jingyu Zhang Heng Song Meiqi Wang Suwen Su Zhenchuan Song |
| author_sort | Bin Xu |
| collection | DOAJ |
| description | ABSTRACTDoxorubicin (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. |
| first_indexed | 2024-03-07T19:47:24Z |
| format | Article |
| id | doaj.art-6ee615ef7d0742078f4618bc67ed51be |
| institution | Directory Open Access Journal |
| issn | 1538-4047 1555-8576 |
| language | English |
| last_indexed | 2024-04-24T05:45:53Z |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Cancer Biology & Therapy |
| spelling | doaj.art-6ee615ef7d0742078f4618bc67ed51be2024-04-23T15:49:56ZengTaylor & Francis GroupCancer Biology & Therapy1538-40471555-85762024-12-0125110.1080/15384047.2024.2321767Role of glutaminyl-peptide cyclotransferase in breast cancer doxorubicin sensitivityBin Xu0Liu Yang1Lixian Yang2Ahmed Al-Maamari3Jingyu Zhang4Heng Song5Meiqi Wang6Suwen Su7Zhenchuan Song8Department of Breast Center, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Breast Center, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Breast Surgery, Xingtai People’s Hospital, Xingtai, Hebei, ChinaDepartment of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Breast Center, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Radiotherapy, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Breast Center, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Breast Center, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaABSTRACTDoxorubicin (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.https://www.tandfonline.com/doi/10.1080/15384047.2024.2321767Breast cancerQPCTMTDH/NF-κB axisdoxorubicinsensitivity |
| spellingShingle | Bin Xu Liu Yang Lixian Yang Ahmed Al-Maamari Jingyu Zhang Heng Song Meiqi Wang Suwen Su Zhenchuan Song Role of glutaminyl-peptide cyclotransferase in breast cancer doxorubicin sensitivity Cancer Biology & Therapy Breast cancer QPCT MTDH/NF-κB axis doxorubicin sensitivity |
| title | Role of glutaminyl-peptide cyclotransferase in breast cancer doxorubicin sensitivity |
| title_full | Role of glutaminyl-peptide cyclotransferase in breast cancer doxorubicin sensitivity |
| title_fullStr | Role of glutaminyl-peptide cyclotransferase in breast cancer doxorubicin sensitivity |
| title_full_unstemmed | Role of glutaminyl-peptide cyclotransferase in breast cancer doxorubicin sensitivity |
| title_short | Role of glutaminyl-peptide cyclotransferase in breast cancer doxorubicin sensitivity |
| title_sort | role of glutaminyl peptide cyclotransferase in breast cancer doxorubicin sensitivity |
| topic | Breast cancer QPCT MTDH/NF-κB axis doxorubicin sensitivity |
| url | https://www.tandfonline.com/doi/10.1080/15384047.2024.2321767 |
| work_keys_str_mv | AT binxu roleofglutaminylpeptidecyclotransferaseinbreastcancerdoxorubicinsensitivity AT liuyang roleofglutaminylpeptidecyclotransferaseinbreastcancerdoxorubicinsensitivity AT lixianyang roleofglutaminylpeptidecyclotransferaseinbreastcancerdoxorubicinsensitivity AT ahmedalmaamari roleofglutaminylpeptidecyclotransferaseinbreastcancerdoxorubicinsensitivity AT jingyuzhang roleofglutaminylpeptidecyclotransferaseinbreastcancerdoxorubicinsensitivity AT hengsong roleofglutaminylpeptidecyclotransferaseinbreastcancerdoxorubicinsensitivity AT meiqiwang roleofglutaminylpeptidecyclotransferaseinbreastcancerdoxorubicinsensitivity AT suwensu roleofglutaminylpeptidecyclotransferaseinbreastcancerdoxorubicinsensitivity AT zhenchuansong roleofglutaminylpeptidecyclotransferaseinbreastcancerdoxorubicinsensitivity |