Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

ANKRD22 enhances cancer stem cell growth and cisplatin resistance in cervical cancer via NUSAP1/Wnt/β-catenin pathway

Dan Pan¹, Wenwei Ye¹, Xiaoxiao Qiu¹, Yaxian Wang²

¹Department of Gynecology, Taizhou Municipal Hospital affiliated with Taizhou University, Taizhou, Zhejiang Province 318000, China; ²Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province 361003, China.

For correspondence:- Yaxian Wang Email:

Accepted: 24 February 2023 Published: 31 March 2023

Citation: Pan D, Ye W, Qiu X, Wang Y. ANKRD22 enhances cancer stem cell growth and cisplatin resistance in cervical cancer via NUSAP1/Wnt/β-catenin pathway. Trop J Pharm Res 2023; 22(3):499-508 doi: 10.4314/tjpr.v22i3.6

© 2023 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate the role of ankyrin repeat domain 22 (ANKRD22) and nucleolar spindle-associated protein 1 (NUSAP1)-mediated Wnt/β-catenin pathway in cervical cancer (CC).

Methods: ANKRD22 levels were evaluated in tissue samples collected from CC patients. The CC cells were transfected with an ANKRD22 silencing vector. Cell proliferation and migration were determined via colony formation, BrdU, scratch and Transwell assays. Sphere formation test was performed to determine the effect of ANKRD22 on the cancer stem cell (CSC)-like traits of CC cells. The effect of ANKRD22 on CSC-like traits was further evaluated by determining the expressions of the CSC markers, Oct4, SOX2, and Nanog, while cisplatin resistance was assessed by CCK-8 assay. The effect of ANKRD22 on the NUSAP1-mediated Wnt/β-catenin pathway was evaluated by determining the expression levels of β-catenin, matrix metalloproteinase-7, and adenomatous polyposis coli. Moreover, ANKRD22-mediated tumor growth was monitored in vivo using an animal model.

Results: ANKRD22 was overexpressed in cancer tissues from CC patients (p < 0.05). ANKRD22 knockdown suppressed CC cell proliferation, migration, invasion, and CSC traits, and also positively regulated Wnt/β-catenin pathway through NUSAP1 (p < 0.05). However, the inhibition of ANKRD22 suppressed tumor growth in vivo through NUSAP1. In addition, the silencing of ANKRD22 alleviated cisplatin resistance in CC cells (p < 0.05).

Conclusion: ANKRD22 activates NUSAP1/Wnt/β-catenin pathway, and enhances CSC-like characteristics and cisplatin resistance, thus exacerbating the malignant behaviors of CC cells. Therefore, ANKRD22 could serve as a promising target for CC treatment.

Keywords: Cervical cancer, Cancer stem cells, Ankyrin repeat domain 22, Nucleolar spindle-associated protein 1/Wnt/&; catenin pathway, Cell migration