METTL1-mediated m7G modification of NEK1 mRNA promotes the proliferation of oral squamous cell carcinoma

Yuan Chen; Xinyu Zhang; Min Li; Bo Fu; Huimin Li; Fengjiao Yuan; Guangyao Li; Qingcui Song

doi:10.1016/j.bbadis.2025.167961

METTL1-mediated m7G modification of NEK1 mRNA promotes the proliferation of oral squamous cell carcinoma

Biochim Biophys Acta Mol Basis Dis. 2025 Jun 23;1871(7):167961. doi: 10.1016/j.bbadis.2025.167961. Online ahead of print.

Authors

Yuan Chen¹, Xinyu Zhang¹, Min Li², Bo Fu², Huimin Li³, Fengjiao Yuan⁴, Guangyao Li⁵, Qingcui Song⁶

Affiliations

¹ School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China.
² Department of Precision Biomedical Key Laboratory, Liaocheng People's Hospital, China; Shandong Provincial Key Medical and Health Laboratory of Precision Medicine for Aging Intervention and Active Health, Liaocheng, China.
³ Department of Oncology, Liaocheng People's Hospital, Liaocheng, Shandong, China.
⁴ Joint Laboratory for Translational Medicine Research, Liaocheng People's Hospital, Liaocheng, Shandong, PR China.
⁵ Department of Hematology, Liaocheng People's Hospital, Liaocheng, Shandong, China.
⁶ School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China; Department of Oncology, Liaocheng People's Hospital, Liaocheng, Shandong, China. Electronic address: sqc0220@126.com.

PMID: 40562282
DOI: 10.1016/j.bbadis.2025.167961

Abstract

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor found in the head and neck region, representing a significant public health concern. The 7-methylguanylate (m7G) RNA modification is a newly recognized regulatory mechanism influencing gene expression, and methyltransferase-like 1 (METTL1) has been linked to tumor progression in various cancers; however, its specific role in OSCC remains largely unexplored. This study reveals that METTL1 expression is notably increased in OSCC and correlates with a poor prognosis for patients. Functional assays indicate that reducing METTL1 levels inhibits OSCC cell proliferation both in laboratory settings and in animal models, resulting in a G1 phase cell cycle arrest. To delve deeper into the mechanisms at play, we utilized m7G Methylated RNA Immunoprecipitation Sequencing (m7G MeRIP-seq) alongside RNA sequencing (RNA-seq) to pinpoint the downstream targets of METTL1 in OSCC cells. Our results confirm that METTL1-catalyzed m7G modification on the 5' untranslated region (5'UTR) of NEK1 mRNA enhances its stability and positively regulates NEK1 expression. Additionally, silencing NEK1 also inhibits OSCC cell proliferation, diminishes clonogenic formation, and induces G1 phase cell cycle arrest. These findings indicate that METTL1-mediated m7G modification is vital for OSCC proliferation, with NEK1 identified as a significant downstream target. In conclusion, METTL1 stands out as a potential prognostic marker and therapeutic target in OSCC, highlighting the need for further exploration of its molecular mechanisms and clinical implications.

Keywords: METTL1; NEK1; Oncogenic signaling; Oral squamous cell carcinoma; m7G RNA modification; mRNA stability.