2. Academic Validation
  3. METTL3-mediated m6A modification of PAK6 drives cervical cancer progression through activating MAPK14

METTL3-mediated m6A modification of PAK6 drives cervical cancer progression through activating MAPK14

  • Int J Biol Macromol. 2025 May;309(Pt 2):142880. doi: 10.1016/j.ijbiomac.2025.142880.
Zhi-Man Zhu 1,  Fu-Chun Huo 1,  Ce Shi 2,  Meng-Ting Li 1,  Yun Zhou 3,  Lan-Sheng Zhang 4,  Dong-Sheng Pei 5
Affiliations

Affiliations

  • 1 Department of Pathology, Xuzhou Medical University, 209 Tong-shan Road, Xuzhou 221004, Jiangsu, China.
  • 2 Nanjing Drum Tower Hospital & Group's Suqian Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210000, Jiangsu, China.
  • 3 Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou 221000, Jiangsu, China. Electronic address: zhouyunxzch@yeah.com.
  • 4 Department of Oncological Radiotherapy, the Second Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu, China. Electronic address: lanshengyan@163.com.
  • 5 Department of Pathology, Xuzhou Medical University, 209 Tong-shan Road, Xuzhou 221004, Jiangsu, China. Electronic address: dspei@xzhmu.edu.cn.
PMID: 40194572 DOI: 10.1016/j.ijbiomac.2025.142880
Abstract

N6-methyladenosine (m6A) is the most prevalent epitranscriptomic modification in mammalian mRNA. Recent studies have revealed that m6A modification is involved in cervical Cancer (CC) pathogenesis, yet the precise mechanisms remain largely unexplored. In this study, we identified DDX5 as a binding partner of the methyltransferase METTL3 in CC cells, demonstrating that DDX5 interacts with METTL3 to regulate global m6A levels. Additionally, METTL3-mediated m6A modification stabilizes PAK6 mRNA through recognition by the m6A reader IGF2BP1. Gain- and loss-of-function studies revealed that PAK6 enhances the proliferation, migration and invasion capability of CC cells by phosphorylating MAPK14 at the Ser56 residue. In vivo experiments further corroborated that METTL3 promotes CC growth and metastasis by upregulating PAK6. Notably, a positive correlation between METTL3 and PAK6 expression is observed in clinical specimens of CC. Collectively, our findings highlight the critical role of METTL3/PAK6 axis in driving CC progression, offering potential therapeutic targets for patients with CC.

Keywords

Cervical cancer; MAPK14; PAK6; m6A modification.

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