Knockdown of BMI1 Enhances The Sensitivity of Cervical and Endometrial Cancer Cells to Paclitaxel
10.16476/j.pibb.2023.0207
- VernacularTitle:BMI1基因下调使宫颈癌和子宫内膜癌对紫杉醇敏感
- Author:
Yi-Ting ZHAO
1
;
Yan LIN
2
;
Wei-Li YANG
3
;
Jun CHEN
1
Author Information
1. Department of Chemoradiotherapy, the Affiliated People’s Hospital of Ningbo University, Ningbo 315000, China
2. Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Health Science Center of Ningbo University, Ningbo 315000, China
3. Department of Gynecology, the Affiliated People’s Hospital of Ningbo University, Ningbo 315000, China
- Publication Type:Journal Article
- Keywords:
cervical cancer;
endometrial cancer;
BMI1;
Bcl-2;
paclitaxel
- From:
Progress in Biochemistry and Biophysics
2024;51(4):924-943
- CountryChina
- Language:English
-
Abstract:
ObjectiveTo study the effects of BMI1 on the proliferation and drug resistance of cervical cancer (CC) and endometrial cancer (EC) cells. In addition, the mechanism of paclitaxel (PTX) resistance induced by BMI1 was explored. MethodsIn this study, we utilized the GTEx, Cbioportal, TCGA, and CPTAC databases to comprehensively analyze the mutation rate as well as mRNA and protein expression profiles of BMI1 in CC and EC. Subsequently, immunohistochemistry (IHC) analysis was employed to evaluate the protein expression levels of BMI1 in 40 pairs of CC and 40 pairs of EC tissue samples. Western blot was conducted to investigate alterations in downstream factor protein levels upon BMI1 knockdown in CC and EC cells. Furthermore, functional experiments were performed to elucidate the role of BMI1 in CC and EC cells. Finally, we assessed the synergistic anti-growth effect by combining BMI1 knockdown with paclitaxel treatment in vitro. ResultsThe Cbioportal database revealed that BMI1 amplification, misinterpretation, and splicing occurred in 1.5% of CC patients and 1.9% of EC patients. Mining the data from TCGA and CPTAC databases, high mRNA levels of BMI1 were associated with the pathological type of CC and lower overall survival, and high protein levels of BMI1 were related to EC’s pathological type and tumor grade. Furthermore, the BMI1 protein level is overexpressed in cancer tissues of CC and EC compared with normal tissues, as detected by IHC analysis. Besides, drug sensitivity experiments showed that overexpression of BMI1 resulted in decreased sensitivity of HeLa and HEC-1-A cells to a variety of anticancer drugs, including paclitaxel. In order to further analyze the relationship between BMI1 and paclitaxel resistance, Western blot was used to detect the changes in the protein levels of downstream factors of BMI1 in HeLa and HEC-1-A cells after BMI1 knockdown. The results showed that the level of anti-apoptotic factor Bcl-2 protein decreased, while that of pro-apoptotic factor BAX increased with BMI1 knockdown. Additionally, we showed that high expression of BMI1 promoted the proliferation and migration of CC and EC cells in vitro. Moreover, CC and EC cells with low BMI1 expression were more sensitive to the paclitaxel. ConclusionThe expression of BMI1 is significantly upregulated in tumor tissues from patients with cervical and endometrial cancer, and silencing BMI1 makes CC and EC cells more sensitive to paclitaxel via enhancing pro-apoptotic regulation.
