METTL3 facilitates the progression of cervical cancer by m6A modification-mediated upregulation of NEK2 - Research summary

Sep 21, 2026

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N6-methyladenosine (m6A) is a major eukaryotic RNA modification, but its mechanism in cervical cancer tumorigenesis remains unclear. This study identifies METTL3 as significantly upregulated in cervical cancer tissues and cell lines. METTL3 knockdown reduces cervical cancer cell growth, migration, and invasion and alters apoptosis, while METTL3 overexpression reverses these effects. MeRIP-seq and Ribo-seq after METTL3 silencing identify NEK2 as an m6A-dependent target, forming a METTL3-NEK2 axis that activates Wnt/β-catenin and suppresses apoptosis.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

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METTL3 in cervical cancer progression

m6A-dependent regulation and target identification

NEK2 function and METTL3-NEK2 axis

Pathway effects on Wnt/β-catenin and apoptosis

Materials and methods

RNA-seq, microarray, and bioinformatics analysis

Clinical sample collection

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN METTL3 facilitates the progression of cervical cancer by m6A modification-mediated upregulation of NEK2 Yilin Guo1,2, Yangyang Bai3, Lu Wang1,2, Zhen Xu1,2􀀍, Nan Zhang1, Wuliang Wang1,2 & Hu Zhao1,2􀀍 N6-methyladenosine (m6A) is the most prevalent modification found in eukaryotic RNA and played a significant role in various cancers. However, the mechanism by which m6A modification influences cervical cancer (CC) tumorigenesis remains unclear. Therefore, we aim to elucidate the role and mechanism of METTL3 in CC progression. In the present study, we observed a significant upregulation of METTL3 in CC tissues and cell lines. Knockdown of METTL3 resulted in reduced growth, migration, and invasion of CC cells, as well as affected apoptosis, while overexpression of METTL3 reversed these effects. Through a combined analysis of meRIP-seq and Ribo-seq data following METTL3 knockdown, NEK2 was identified as a key target of METTL3 in CC cells. Correlation analysis, MeRIPqPCR, and luciferase reporter assay suggested that METTL3 regulates NEK2 expression through m6A modification. NEK2 synergized with METTL3 to mediate the malignant phenotype of CC cells. The METTL3-NEK2 axis promoted CC progression by activating the Wnt/β-catenin pathway and inhibiting the apoptosis pathway. In conclusion, METTL3 facilitated the malignant progression of CC and contributed to the formation of the METTL3-NEK2 regulatory axis in an m6A-dependent manner, which represented a potential target for CC therapy. Keywords Cervical cancer, N6-methyladenosine, METTL3, NEK2 Cervical cancer (CC) remains the fourth most common gynecological malignant tumor, with approximately 341,831 deaths and 604,127 new cases each year in worldwide1. The morbidity rate of CC is steadily declining in developed countries, attributed to the widespread implementation of the HPV vaccine and cervical cancer screening2. However, in developing countries, the mortality rate from CC has not decreased to the desired level, primarily due to poor public awareness, limited screening coverage, and challenges faced by women living in remote areas3. Patients diagnosed with CC at an early stage who receive prompt treatment exhibit a better prognosis; conversely, the prognosis for recurrent and metastatic CC remains unsatisfactory4,5. Consequently, it is essential to identify novel therapeutic targets to reduce CC mortality and enhance the survival of patients with this disease. N6-methyladenosine (m6A) modification plays a crucial role in RNA stability, splicing, translocation, and nuclear localization, all of which are vital for tumor proliferation, invasion, and metastasis6. The m6A modification process is primarily mediated by methyltransferases (writers), demethylases (erasers), and reading proteins (readers)7. Recent studies have revealed that the demethylase ALKBH5 is associated with distant metastasis and lymph node metastasis in gastric cancer8. METTL3, a methyltransferase, catalyzes the formation of m6A modifications9. In recent years, the potential of METTL3 as a tumor biomarker has been identified in various malignant tumors. For example, METTL3 inhibits the expression of SOCS2 through the reading protein YTHDF2, thereby promoting the proliferation and metastasis of hepatocellular carcinoma10. Unfortunately, the mechanism by which METTL3 mediates m6A modification in CC remains unclear. NEK2, a member of the Never in Mitosis A (NIMA)-related kinases family, is involved in various cellular functions, including cell cycle control, centrosome organization, DNA damage response, and RNA splicing11. Increasing evidence indicates that NEK2 is overexpressed in various malignant tumors, particularly in CC12. 1Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Zhengzhou University, 450014 Zhengzhou, China. 2Henan Gynecological diseases (Gynecology Oncology) Clinical Research Center, 4500

FAQs

What is the main research question about METTL3 in cervical cancer?

The study investigates how m6A modification mediated by METTL3 influences cervical cancer progression and tumorigenesis, which was previously unclear.

How does altering METTL3 expression affect cervical cancer cells?

METTL3 knockdown reduces cervical cancer cell growth, migration, and invasion and affects apoptosis, while METTL3 overexpression reverses these changes.

How was NEK2 identified and what is its role?

Combined MeRIP-seq and Ribo-seq data after METTL3 knockdown identified NEK2 as a key target; assays support m6A-dependent regulation of NEK2, and NEK2 synergizes with METTL3 to drive the malignant phenotype.

Sep 21, 2026

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