Title
Author
DOI
Article Type
Special Issue
Volume
Issue
CENPU affects the paclitaxel resistance of cervical cancer cells by regulating the FOXM1/ABCC5 pathway
1Department of Pathology, Zhaoqing Medical College, 526020 Zhaoqing, Guangdong, China
DOI: 10.22514/ejgo.2024.014 Vol.45,Issue 1,February 2024 pp.89-95
Submitted: 24 August 2023 Accepted: 13 November 2023
Published: 15 February 2024
*Corresponding Author(s): Xia Zhang E-mail: Zhangxia_668@163.com
In cervical cancer (CC), the efficacy of chemotherapy is often hindered by the development of paclitaxel (PTX) resistance, even in patients who initially responded to chemotherapy. However, the mechanisms underlying PTX resistance in CC patients remain unclear. In this study, we uncover a unique role played by CENPU (centromeric protein U, also known as PBIP1/KLIP1/CENP-50/MLF1IP) in association with paclitaxel resistance in CC cells. First, we established paclitaxel-resistant cell lines from Hela and SiHa cells (designated as Hela/PTX and SiHa/PTX) and confirmed their resistance by determining the half-maximal inhibitory concentration (IC50) values and assessing cell viability. The results demonstrated that Hela/PTX and SiHa/PTX cells exhibited an elevated IC50 and enhanced cell proliferation, accompanied by a decrease in apoptosis. Subsequently, si-CENPU was used to silence CENPU in Hela/PTX and SiHa/PTX cells, which led to a reduction in cell viability and an increase in cell apoptosis, indicating that the silencing of CENPU mitigated paclitaxel resistance in Hela/PTX and SiHa/PTX cells. Furthermore, CENPU knockdown suppressed Forkhead box M1 (FOXM1) and Adenosine Triphosphate (ATP) binding cassette subfamily C member 5 (ABCC5) expression in Hela/PTX and SiHa/PTX cells. Interestingly, the alleviating effects of CENPU silencing on paclitaxel resistance in CC cells were compromised when FOXM1 levels were supplemented, indicating that CENPU knockdown could attenuate PTX resistance by downregulating the FOXM1/ABCC5 signaling pathway. In conclusion, our study reveals an elevated expression of CENPU in paclitaxel-resistant CC (Hela/PTX and SiHa/PTX) and demonstrates that the knockdown of CENPU can mitigate paclitaxel resistance in CC cells by deregulating the FOXM1/ABCC5 signaling pathway.
Paclitaxel resistance; Cervical cancer; CENPU; FOXM1; ABCC5
Xia Zhang,Yuanyi Zhang,Min Wang. CENPU affects the paclitaxel resistance of cervical cancer cells by regulating the FOXM1/ABCC5 pathway. European Journal of Gynaecological Oncology. 2024. 45(1);89-95.
[1] Pimple S, Mishra G. Cancer cervix: epidemiology and disease burden. Cytojournal. 2022; 19: 21.
[2] Ito F, Nomura H, Ito M, Takahashi K, Fujii T, Hayashi S. Concurrent chemoradiotherapy and salvage chemotherapy for advanced cervical cancer with a pedunculated cervical leiomyoma: a case report. European Journal of Gynaecological Oncology. 2022; 43; 100–103.
[3] Kasamatsu T, Arimoto T. Phase III clinical trials of radical hysterectomy with minimal parametrectomy for patients with early-stage cervical cancer: a review. European Journal of Gynaecological Oncology. 2022; 43; 12–18.
[4] XiongH, Yi T, Hu JM, Zeng HY, Liu LJ, Zhou HY. A survey of lymph node involvement under preoperative medical imaging in cervical cancer patients. European Journal of Gynaecological Oncology. 2022; 43; 36–41.
[5] Sharifi-Rad J, Quispe C, Patra JK, Singh YD, Panda MK, Das G, et al. Paclitaxel: application in modern oncology and nanomedicine-based cancer therapy. Oxidative Medicine and Cellular Longevity. 2021; 2021: 3687700.
[6] Long X, Zheng M, Yang Y, Chen Y, Zhang X, Zhang H. Circ_ZFR is linked to paclitaxel resistance in cervical cancer via miR-944 sponging and IL-10 upregulation. Analytical Cellular Pathology. 2022; 2022: 4807287.
[7] Modi A, Purohit P, Roy D, Vishnoi JR, Pareek P, Elhence P, et al. FOXM1 mediates GDF-15 dependent stemness and intrinsic drug resistance in breast cancer. Molecular Biology Reports. 2022; 49: 2877–2888.
[8] Zhou D, Liu J, Liu F, Luo G, Li H, Zhang R, et al. A novel FoxM1-PSMB4 axis contributes to proliferation and progression of cervical cancer. Biochemical and Biophysical Research Communications. 2020; 521: 746–752.
[9] Hou Y, Dong Z, Zhong W, Yin L, Li X, Kuerban G, et al. FOXM1 promotes drug resistance in cervical cancer cells by regulating ABCC5 gene transcription. BioMed Research International. 2022; 2022: 3032590.
[10] Kashgari FK, Ravna A, Sager G, Lysa R, Enyedy I, Dietrichs ES. Identification and experimental confirmation of novel cGMP efflux inhibitors by virtual ligand screening of vardenafil-analogues. Biomedicine & Pharmacotherapy. 2020; 126: 110109.
[11] Zhang Y, Zhang W, Sun L, Yue Y, Shen D, Tian B, et al. HJURP inhibits proliferation of ovarian cancer cells by regulating CENP-A/CENP-N. Bull Cancer. 2022; 109: 1007–1016.
[12] Zhao S, Geng Y, Cao L, Yang Q, Pan T, Zhou D, et al. Deciphering the performance of polo-like kinase 1 in triple-negative breast cancer progression according to the centromere protein U-phosphorylation pathway. American Journal of Cancer Research. 2021; 11: 2142–2158.
[13] Zhang Q, Li YD, Zhang SX, Shi YY. Centromere protein U promotes cell proliferation, migration and invasion involving Wnt/beta-catenin signaling pathway in non-small cell lung cancer. European Review for Medical and Pharmacological Sciences. 2018; 22: 7768–7777.
[14] Yu Y, Chen X, Zhang W, Liu J. Abnormal expression of centromere protein U is associated with hepatocellular cancer progression. BioMed Research International. 2021; 2021: 4051192.
[15] Wang X, Chen D, Gao J, Long H, Zha H, Zhang A, et al. Centromere protein U expression promotes non-small-cell lung cancer cell proliferation through FOXM1 and predicts poor survival. Cancer Management and Research. 2018; 10: 6971–6984.
[16] Qu Y, Song L, Xu S, Yu MSY, Kadioglu O, Michelangeli F, et al. Pomiferin targets SERCA, mTOR, and P-gp to induce autophagic cell death in apoptosis-resistant cancer cells, and reverses the MDR phenotype in cisplatin-resistant tumors in vivo. Pharmacological Research. 2023; 191: 106769.
[17] Zhu Y, Yu F, Jiao Y, Feng J, Tang W, Yao H, et al. Reduced miR-128 in breast tumor-initiating cells induces chemotherapeutic resistance via Bmi-1 and ABCC5. Clinical Cancer Research. 2011; 17: 7105–7115.
[18] Zhang X, Wang M, Zhang Y, Yang J, Duan W. Knockdown of CENPU inhibits cervical cancer cell migration and stemness through the FOXM1/Wnt/beta-catenin pathway. Tissue and Cell. 2023; 81: 102009.
[19] Liu Y, Yao Y, Liao B, Zhang H, Yang Z, Xia P, et al. A positive feedback loop of CENPU/E2F6/E2F1 facilitates proliferation and metastasis via ubiquitination of E2F6 in hepatocellular carcinoma. International Journal of Biological Sciences. 2022; 18: 4071–4087.
[20] Deng T, Jiang X, He Z, Cai M, Chen C, Xu Z. Centromere protein U (CENPU) promotes gastric cancer cell proliferation and glycolysis by regulating high mobility group box 2 (HMGB2). Bioengineered. 2021; 12: 10194–10202.
Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.
Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.
Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.
JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.
Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.
BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.
Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.
Top