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ORIGINAL RESEARCH ARTICLE

MiR-381-3p/TET3 axis promotes cervical cancer: A bioinformatic integrative analysis

Hilda Jiménez Wences1,2† ,  Pedro Antonio Ávila López3† ,  Gabriela Elizabeth Campos Viguri1,2 ,  Ana Elvira Zacapala Gómez4 ,  Julio Ortíz Ortíz4 ,  Verónica Antonio Vejar4 ,  Francisco Israel Torres Rojas4 ,  Eric Genaro Salmerón Bárcenas3*
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1 Clinical Research Laboratory, Faculty of Chemical-Biological Sciences, Autonomous University of Guerrero, Chilpancingo, Guerrero, Mexico
2 Biomolecule Research Laboratory, Faculty of Chemical-Biological Sciences, Autonomous University of Guerrero, Chilpancingo, Guerrero, Mexico
3 Department of Molecular Biomedicine, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-I.P.N.) City, Mexico
4 Molecular Biomedicine Laboratory, Faculty of Chemical-Biological Sciences, Autonomous University of Guerrero, Chilpancingo, Guerrero, Mexico
CP 2024, 6(3), 3884
Submitted: 6 June 2024 | Accepted: 5 August 2024 | Published: 12 September 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Cervical cancer (CC) is a global public health problem. Epigenetic factors, such as microRNAs, play a key role in the development of CC. Although a previous study reported that miR-381-3p inhibits CC by downregulating fibroblast growth factor 7, its role in CC remains largely unknown. This study aimed to fill the gap by analyzing the role of miR-381-3p in CC. Expression analysis was performed using databases including The Cancer Genome Atlas, Gene Expression Omnibus, and the Human Protein Atlas. Receiver operating characteristics and Kaplan–Meier curves were plotted using GraphPad Prism and Kaplan–Meier Plotter databases. Target messenger RNAs were identified using the miRDB and miRPathDB databases. Kyoto Encyclopedia of Genes and Genomes, Gene Ontology Biological Process, and Gene Set Enrichment Analysis were performed using Enrichr and WebGestalt databases. Mutation analysis was conducted using the cBioPortal database. In this study, we found that miR-381-3p expression is low in CC. Moreover, we identified a total of 1,191 potential targets of miR-381-3p that may be involved in key signaling pathways in this cancer. Interestingly, our results identified ten-eleven translocation 3 (TET3) as a potential target, with evidence suggesting that TET3 expression is increased in CC. This increase in TET3 expression may be useful as a diagnostic and prognostic biomarker. In addition, four mutations were identified in the TET3 protein. TET3 expression increases in patients with International federation of gynecology and obstetrics stage II CC and in those with lymph node metastasis. Mechanistically, TET3 expression may be induced by a gain in copy number, human papillomavirus infection, aberrant methylation, and activation of the transcription factor activator protein 2α. Finally, we identified 145 genes that are regulated by TET3 in CC, which are involved in key pathways and biological processes associated with CC, such as the cell cycle, DNA replication, mitogen-activated protein kinase signaling pathway, and basal transcription factors. In conclusion, we identified the miR-381-3p/TET3 axis as a key player in the carcinogenic process of CC.

Keywords
miR-381-3p
Ten-eleven translocation 3
Cervical cancer
Bioinformatic analysis
Funding
None.
Conflict of interest
The authors declare they have no competing interests.
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