FTO Facilitates Cervical Cancer Malignancy Through Inducing m6A-Demethylation of PIK3R3 mRNA

Sep 21, 2026

FTO promotes malignant progression in cervical cancer through epigenetic regulation of m6A. The study evaluates clinical relevance by comparing FTO expression between HPV-positive and HPV-negative patients and by verifying FTO protein levels in cervical cancer versus paracancerous tissues using IHC. Lentiviral modulation of FTO assesses cell proliferation, migration, and invasion in vitro and in vivo, while Merip-seq/Merip-qPCR profile m6A changes and identify the FoxO pathway activation linked to PIK3R3.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages14

Reading Time35 min

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Abstract

Background and Aims

Materials & Methods

Results

Conclusion

Introduction

Epigenetic regulation and m6A

FoxO pathway and PIK3R3

Cancer Medicine RESEARCH ARTICLE OPEN ACCESS FTO Facilitates Cervical Cancer Malignancy Through Inducing m6A-Demethylation ofPIK3R3 mRNA Bingxin Chen1,2 | Liming Wang1,2 | Xiaomin Li1 | Ci Ren1 | Chun Gao1 | Wencheng Ding1 | Hui Wang1,2 1Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China | 2Department of Gynecologic Oncology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China Correspondence: Hui Wang ([huit71@sohu.com](huit71@sohu.com)) Received: 21 December 2023 | Revised: 9 July 2024 | Accepted: 4 November 2024 Funding: This study was funded by grants from the National Natural Science Foundation of China (81830074) and the Natural Science Foundation of Zhejiang Province (No. LQ23H160033) . Keywords: cervical carcinoma | FTO | m6A | malignancy | PIK3R3 ABSTRACT Background: The incidence rate and mortality of cervical cancer rank the fourth in the global female cancer. N6-methyladenosine (m6A) always plays an important role in tumor progression, and fat mass and obesity-associated gene (FTO) works as the m6Ademethylase. Aims: Our study aimed to narrate the biological function and potential mechanisms for FTO in cervical cancer malignancy. Materials & Methods: We analyzed potential clinical value of FTO in cervical cancer patients. The relative protein levels of FTO in cervical cancerous tissue and paracancerous tissue were verified by IHC. After changing the FTO expression level by lentivirus transfection, the proliferation and metastasis ability of cervical cancer cells were detected both in vitro and in vivo. Further, Merip-seq and Merip-qPCR are used to profile m6A transcriptome-wide. Finally, western blot were performed to identify the regulatory mechanism. Results: Based on TCGA-CESC cohort and GEO dataset, FTO expression levels in HPV-positive cancer patients were significantly higher than those in HPV-negative cancer patients and could predict advanced FIGO stage. The protein level of FTO in cervical cancerous tissue was higher than that in paracancerous tissue. Functional assays indicated that FTO promoted the proliferation, migration and invasion of cervical cancer cells both in vitro and in vivo. The Merip-seq and Merip-qPCR evoked that relative PIK3R3 m6A level was significantly increased after FTO knockdown, which effected the activation of FoxO pathway. After knocking down FTO, upregulation of PIK3R3 can restore the malignancy of cervical cancer. Conclusion: All in all, these data suggest a vital role for FTO in occurrence and development of cervical cancer. 1 | Introduction The incidence rate and mortality of cervical cancer rank the fourth in the global female cancer [1]. The 5-year survival rate of patients with advanced cervical cancer is less than 20%[2–4]. The main factors affecting the survival are inevitable recurrence and metastasis [5–7]. The growing evidence displayed that the cervical cancer progression was a complex process, which involved the changes in the levels of genetics, epigenetics and transcriptomics [8, 9]. Therefore, the factors associated with cervical cancer malignancy are the hot candidates in cervical cancer, which might provide new ideas for early diagnosis and targeted therapy. Epigenetic regulation plays an important role in the biological behavior of malignant tumor. N6-methyladenosine (m6A) modification is an important epigenetic regulations, and work as a crucial regulator for gene expression at the post-transcriptional level [10–13]. There are three major kinds of enzymes involved This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd. Cancer Medicine, 2024; 13:e70507 1 of 14 [https://doi.org/10.1002/cam4.70

FAQs

What is the main biological role of FTO proposed in cervical cancer?

FTO is proposed to facilitate cervical cancer malignancy by inducing m6A demethylation, thereby influencing downstream gene regulation and tumor-promoting signaling.

How was FTO-related clinical significance evaluated?

FTO expression was compared across HPV-positive versus HPV-negative patient groups using analyses from TCGA-CESC and GEO, and the protein level differences were verified in tissue samples by IHC.

What mechanism connects FTO to cervical cancer malignancy?

FTO knockdown alters m6A levels of PIK3R3, which affects FoxO pathway activation; conversely, restoring PIK3R3 upregulation can rescue malignancy phenotypes after FTO suppression.

Sep 21, 2026

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