EBF1 Promotes the Sensitivity of Cervical Cancer Cells to Cisplatin via Activating FBN1 Transcription
- Авторлар: Shen N.1, Lin J.2, Liu P.2
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Мекемелер:
- Department of Pharmacy, Ganzhou Women and Children’s Health Care Hospital, Ganzhou
- Department of Pharmacy, the First Affiliated Hospital of Gannan Medical University
- Шығарылым: Том 57, № 3 (2023)
- Беттер: 503-504
- Бөлім: МОЛЕКУЛЯРНАЯ БИОЛОГИЯ КЛЕТКИ
- URL: https://journals.rcsi.science/0026-8984/article/view/138633
- DOI: https://doi.org/10.31857/S0026898423030102
- EDN: https://elibrary.ru/CHKZXJ
- ID: 138633
Дәйексөз келтіру
Аннотация
Cisplatin (DDP) is widely used in the chemotherapy of cervical cancer (CC), the fourth most common female malignancy worldwide. However, some patients progress to chemotherapy resistance, which leads to chemotherapy failure, tumor recurrence, and poor prognosis. Therefore, strategies to identify the regulatory mechanisms underlying CC development and increase tumor sensitivity to DDP will help improve patient survival. This research was designed to ascertain the mechanism of EBF1-dependent regulation of FBN1 which promotes chemosensitivity of CC cells. The expression of EBF1 and FBN1 was measured in CC tissues resistant or sensitive to chemotherapy and in DDP-sensitive or -resistant cells (SiHa and SiHa-DDP cells). SiHa-DDP cells were transduced with lentiviruses encoding EBF1 or FBN1 to evaluate the influence of these two proteins on cell viability, expression of MDR1 and MRP1, and cell aggressiveness. Moreover, the interaction between EBF1 and FBN1 was predicted and demonstrated. Finally, to further verify the EBF1/FB1-dependent mechanism of DDP sensitivity regulation in CC cells a xenograft mouse model of CC was established using SiHa-DDP cells transduced with lentiviruses carrying EBF1 gene and shRNA directed to FBN1.EBF1 and FBN1 showed decreased expression in CC tissues and cells, particularly in those resistant to chemotherapy. Transduction of SiHa-DDP cells with lentiviruses encoding EBF1 or FBN1 lead to decreased viability, IC50, proliferation capacity, colony formation ability, aggressiveness, and increased cell apoptosis. We have shown that EBF1 activates FBN1 transcription by binding to FBN1 promoter region. Additionally, it was revealed that FBN1 silencing reversed the promoting effect of EBF1 overexpression on chemosensitivity of CC cells in vivo. EBF1 facilitated chemosensitivity in CC cells by activating FBN1 transcription.
Негізгі сөздер
Авторлар туралы
N. Shen
Department of Pharmacy, Ganzhou Women and Children’s Health Care Hospital, Ganzhou
Email: liupeipei198603@163.com
P.R. China, 341000, Jiangxi
J. Lin
Department of Pharmacy, the First Affiliated Hospital of Gannan Medical University
Email: liupeipei198603@163.com
P.R. China, 341000, Ganzhou Jiangxi
P. Liu
Department of Pharmacy, the First Affiliated Hospital of Gannan Medical University
Хат алмасуға жауапты Автор.
Email: liupeipei198603@163.com
P.R. China, 341000, Ganzhou Jiangxi