Role of glutaminyl-peptide cyclotransferase in breast cancer doxorubicin sensitivity.

IF 4.4 4区 医学 Q2 ONCOLOGY
Cancer Biology & Therapy Pub Date : 2024-12-31 Epub Date: 2024-02-28 DOI:10.1080/15384047.2024.2321767
Bin Xu, Liu Yang, Lixian Yang, Ahmed Al-Maamari, Jingyu Zhang, Heng Song, Meiqi Wang, Suwen Su, Zhenchuan Song
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引用次数: 0

Abstract

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.

谷氨酰胺酰肽环转酶在乳腺癌多柔比星敏感性中的作用
多柔比星(DOX)是最有效、应用最广泛的化疗药物之一。然而,DOX 耐药性是乳腺癌治疗中的一个关键风险问题。以往的研究表明,偏粘连蛋白(MTDH)参与了乳腺癌的 DOX 耐药性,但其确切机制仍不清楚。本研究发现,谷氨酰肽环转酶(QPCT)是乳腺癌中 MTDH DOX 抗性相关的下游基因。在 GEPIA 数据库、乳腺癌组织和乳腺癌细胞中都发现了 QPCT 的高表达。临床数据显示,QPCT的表达与DOX治疗患者的不良预后呈正相关。QPCT 的过表达可促进 MCF-7 和 MDA-MB-231 细胞的增殖、侵袭和迁移,并降低 DOX 的敏感性。从机理上讲,MTDH正向调控NF-κB(p65)和QPCT的表达,而NF-κB(p65)直接调控QPCT的表达。因此,我们提出了 MTDH/NF-κB (p65)/QPCT 信号轴。总之,我们的研究结果阐明了 MTDH/NF-κB (p65) 轴调控 QPCT 信号转导的机制,并提示该复合物可能在乳腺癌进展中发挥重要作用,并影响 DOX 的敏感性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cancer Biology & Therapy
Cancer Biology & Therapy 医学-肿瘤学
CiteScore
7.00
自引率
0.00%
发文量
60
审稿时长
2.3 months
期刊介绍: Cancer, the second leading cause of death, is a heterogenous group of over 100 diseases. Cancer is characterized by disordered and deregulated cellular and stromal proliferation accompanied by reduced cell death with the ability to survive under stresses of nutrient and growth factor deprivation, hypoxia, and loss of cell-to-cell contacts. At the molecular level, cancer is a genetic disease that develops due to the accumulation of mutations over time in somatic cells. The phenotype includes genomic instability and chromosomal aneuploidy that allows for acceleration of genetic change. Malignant transformation and tumor progression of any cell requires immortalization, loss of checkpoint control, deregulation of growth, and survival. A tremendous amount has been learned about the numerous cellular and molecular genetic changes and the host-tumor interactions that accompany tumor development and progression. It is the goal of the field of Molecular Oncology to use this knowledge to understand cancer pathogenesis and drug action, as well as to develop more effective diagnostic and therapeutic strategies for cancer. This includes preventative strategies as well as approaches to treat metastases. With the availability of the human genome sequence and genomic and proteomic approaches, a wealth of tools and resources are generating even more information. The challenge will be to make biological sense out of the information, to develop appropriate models and hypotheses and to translate information for the clinicians and the benefit of their patients. Cancer Biology & Therapy aims to publish original research on the molecular basis of cancer, including articles with translational relevance to diagnosis or therapy. We will include timely reviews covering the broad scope of the journal. The journal will also publish op-ed pieces and meeting reports of interest. The goal is to foster communication and rapid exchange of information through timely publication of important results using traditional as well as electronic formats. The journal and the outstanding Editorial Board will strive to maintain the highest standards for excellence in all activities to generate a valuable resource.
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