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Current Cancer Drug Targets

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

ZIP14 Affects the Proliferation, Apoptosis, and Migration of Cervical Cancer Cells by Regulating the P38 MAPK Pathway

Author(s): Lixia Jiang*, Ting Xie, Yu Xia, Feng Li, Tianyu Zhong and Mi Lai

Volume 24, Issue 8, 2024

Published on: 21 November, 2023

Page: [779 - 790] Pages: 12

DOI: 10.2174/0115680096250711231024063841

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Abstract

Background: Cervical cancer (CC) remains a major public health concern and is a leading cause of female mortality worldwide. Understanding the molecular basis of its pathogenesis is essential for the development of novel therapeutic strategies. In this study, we aimed to dissect the role of a specific molecule, ZIP14, in the initiation and progression of CC.

Methods: We used Gene Expression Omnibus for target gene identification, while KEGG was used to delineate CC-related pathways. Proliferation, migration, and apoptosis levels in CC cells were assessed using CCK8, Transwell, and flow cytometry, respectively. The effect of the target genes on the in vivo tumorigenesis of CC cells was evaluated using the subcutaneous tumorigenesis assay.

Results: ZIP14 (SLC39A14) was found to be underexpressed in CC samples. Our KEGG pathway analysis revealed the potential involvement of the P38 mitogen-activated protein kinase (MAPK) pathway in CC pathogenesis. Overexpression of ZIP14 in HeLa and Caski cells increased p38 phosphorylation, inhibited cell growth and migration, and enhanced apoptosis. Conversely, ZIP14 knockdown produced the opposite effects. Importantly, the bioeffects induced by ZIP14 overexpression could be counteracted by the p38 MAPK pathway inhibitor SB203580. In vivo experiments further confirmed the influence of ZIP14 on CC cell migration.

Conclusion: Our study is the first to elucidate the pivotal role of ZIP14 in the pathogenesis of CC, revealing its inhibitory effects through the activation of the p38 MAPK signaling pathway. The discovery not only provides a deeper understanding of CC's molecular underpinnings, but also highlights ZIP14 as a promising therapeutic target. As ZIP14 holds significant potential for therapeutic interventions, our findings lay a robust foundation for further studies and pave the way for the exploration of novel treatment modalities for cervical cancer.

Keywords: Cervical cancer, ZIP14, P38 MAPK, GEO, pathogenesis, apoptosis, levels.

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