A microRNA Profile Regulates Inflammation-Related Signaling Pathways in Young Women with Locally Advanced Cervical Cancer

Autor: Oliver Millan-Catalan, Eloy Andrés Pérez-Yépez, Antonio Daniel Martínez-Gutiérrez, Miguel Rodríguez-Morales, Eduardo López-Urrutia, Jaime Coronel-Martínez, David Cantú de León, Nadia Jacobo-Herrera, Oscar Peralta-Zaragoza, César López-Camarillo, Mauricio Rodríguez-Dorantes, Carlos Pérez-Plasencia
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Cells, Vol 13, Iss 11, p 896 (2024)
Druh dokumentu: article
ISSN: 13110896
2073-4409
DOI: 10.3390/cells13110896
Popis: Cervical cancer (CC) remains among the most frequent cancers worldwide despite advances in screening and the development of vaccines against human papillomavirus (HPV), involved in virtually all cases of CC. In mid-income countries, a substantial proportion of the cases are diagnosed in advanced stages, and around 40% of them are diagnosed in women under 49 years, just below the global median age. This suggests that members of this age group share common risk factors, such as chronic inflammation. In this work, we studied samples from 46 patients below 45 years old, searching for a miRNA profile regulating cancer pathways. We found 615 differentially expressed miRNAs between tumor samples and healthy tissues. Through bioinformatic analysis, we found that several of them targeted elements of the JAK/STAT pathway and other inflammation-related pathways. We validated the interactions of miR-30a and miR-34c with JAK1 and STAT3, respectively, through dual-luciferase and expression assays in cervical carcinoma-derived cell lines. Finally, through knockdown experiments, we observed that these miRNAs decreased viability and promoted proliferation in HeLa cells. This work contributes to understanding the mechanisms through which HPV regulates inflammation, in addition to its canonical oncogenic function, and brings attention to the JAK/STAT signaling pathway as a possible diagnostic marker for CC patients younger than 45 years. To our knowledge to date, there has been no previous description of a panel of miRNAs or even ncRNAs in young women with locally advanced cervical cancer.
Databáze: Directory of Open Access Journals
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