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Original Research

Open Access

CENPU affects the paclitaxel resistance of cervical cancer cells by regulating the FOXM1/ABCC5 pathway

  • Xia Zhang1,*,
  • Yuanyi Zhang1
  • Min Wang1

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

Abstract

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.


Keywords

Paclitaxel resistance; Cervical cancer; CENPU; FOXM1; ABCC5


Cite and Share

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.

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