HOTAIR Promotes the Hyperactivation of PI3K/Akt and Wnt/β-Catenin Signaling Pathways via PTEN Hypermethylationin Cervical Cancer

Sep 21, 2026

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Mechanisms supporting sustained PI3K/AKT and Wnt/β-catenin pathway activation mediated by HOTAIR in cervical cancer remain insufficiently characterized. This study investigated pathway crosstalk by modulating HOTAIR expression in HeLa cells, demonstrating HOTAIR as a key regulator that maintains activation of both signaling routes. HOTAIR knockdown or overexpression altered PI3K/AKT and Wnt/β-catenin transcriptional activity. HIF1α was found to directly induce HOTAIR transcription, promoting epigenetic silencing of the PTEN promoter via DNMT1, sustaining pathway hyperactivation and suggesting a HOTAIR/HIF1α regulatory axis driving oncogenic phenotypes.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Introduction

HOTAIR regulation and signaling pathway context

Experimental focus

Modulating HOTAIR in HeLa cells

HIF1α-driven HOTAIR and PTEN epigenetic silencing

cells Article HOTAIR Promotes the Hyperactivation of PI3K/Akt and Wnt/β-Catenin Signaling Pathways via PTEN Hypermethylationin Cervical Cancer Samuel Trujano-Camacho 1,2, David Cantú-de León 2, Eloy Pérez-Yepez 2, Carlos Contreras-Romero 2, Jossimar Coronel-Hernandez 2, Oliver Millan-Catalan 2, Mauricio Rodríguez-Dorantes 3, Cesar López-Camarillo 4, Concepción Gutiérrez-Ruiz 5,6, Nadia Jacobo-Herrera 7 and Carlos Pérez-Plasencia 2,8, * Citation: Trujano-Camacho, S.; Cantú-de León, D.; Pérez-Yepez, E.; Contreras-Romero, C.; CoronelHernandez, J.; Millan-Catalan, O.; Rodríguez-Dorantes, M.; López-Camarillo, C.; Gutiérrez-Ruiz, C.; Jacobo-Herrera, N.; et al. HOTAIR Promotes the Hyperactivation of PI3K/Akt and Wnt/β-Catenin Signaling Pathways via PTEN Hypermethylation in Cervical Cancer. Cells 2024, 13, 1484. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/cells13171484](10.3390/cells13171484) Academic Editor: Alexander E. Kalyuzhny Received: 1 August 2024 Revised: 27 August 2024 Accepted: 29 August 2024 Published: 4 September 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Experimental Biology PhD Program, DCBS, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City 09340, Mexico; [samuel.trujano1@gmail.com](samuel.trujano1@gmail.com) 2 Laboratorio de Genómica, Instituto Nacional de Cancerología, Av. San Fernando 22, Belisario Domínguez Secc 16, Tlalpan, Ciudad de México 14080, Mexico; [dfcantu@gmail.com](dfcantu@gmail.com) (D.C.-d.L.); [eperezy2306@gmail.com](eperezy2306@gmail.com) (E.P.-Y.); [carlos.oncogenomica@gmail.com](carlos.oncogenomica@gmail.com) (C.C.-R.); [jossithunders@gmail.com](jossithunders@gmail.com) (J.C.-H.); [oliver.millan.sg@gmail.com](oliver.millan.sg@gmail.com) (O.M.-C.) 3 Laboratorio de Oncogenómica, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, Mexico; [mrodriguez@inmegen.gob.mx](mrodriguez@inmegen.gob.mx) 4 Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, Ciudad de México 03100, Mexico; [cesar.lopez@uacm.edu.mx](cesar.lopez@uacm.edu.mx) 5 Laboratory of Experimental Medicine, Translational Medicine Unit, Instituto de Investigaciones Biomédicas, UNAM/Instituto Nacional de Cardiología Ignacio Chávez, Tlalpan, Mexico City 14080, Mexico; [mcgr@xanum.uam.mx](mcgr@xanum.uam.mx) 6 Department of Health Sciences, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City 09340, Mexico 7 Unidad de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran, Av. Vasco de Quiroga 15, Col. Belisario Domínguez Sección XVI, Tlalpan, Ciudad de México 14080, Mexico; [nadia.jacoboh@incmnsz.mx](nadia.jacoboh@incmnsz.mx) 8 Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México (UNAM), Tlalnepantla 54090, Mexico * Correspondence: [carlos.pplas@gmail.com](carlos.pplas@gmail.com); Tel.: +52-(55)-5623-1333 (ext. 39807) Abstract: The mechanisms underlying the sustained activation of the PI3K/AKT and Wnt/β-catenin pathways mediated by HOTAIR in cervical cancer (CC) have not been extensively described. To address this knowledge gap in the literature, we explored the interactions between these pathways by driving HOTAIR expression levels in HeLa cells. Our findings reveal that HOTAIR is a key regulator in sustaining the activation of both signaling pathways. Specifically, altering HOTAIR expression—either by knockdown or overexpression—significantly influenced the transcriptional activity of the PI3K/AKT and Wnt/β-catenin pathways. Additionally, we discovered that HIF1α directly induces HOTAIR transcription, which in turn leads to

FAQs

What is the main function of HOTAIR in cervical cancer signaling described in this article?

HOTAIR sustains activation of both the PI3K/AKT and Wnt/β-catenin pathways in cervical cancer, acting as a key regulator of their continued signaling activity.

How were HOTAIR effects on the pathways tested in the study?

The study drove HOTAIR expression levels in HeLa cells and assessed outcomes after HOTAIR knockdown or overexpression, which significantly influenced the pathways’ transcriptional activity.

What links HIF1α to sustained pathway activation according to the findings?

HIF1α directly induces HOTAIR transcription; HOTAIR then contributes to epigenetic silencing of the PTEN promoter via DNMT1, leading to sustained activation of both signaling pathways.

Sep 21, 2026

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