New insights on the interaction between m6A modification and non-coding RNA in cervical squamous cell carcinoma

World Journal of Surgical Oncology

Research

Chen Lin¹  Yongmei Huang²  Cailing Ma³  Guqun Shen⁴  Gulibiya Aizezi⁴  Fen Li⁴  Jinrui Yuan⁴  Yan Wang⁵ 

[1] Department of Pathology, School of Basic Medicine, Xinjiang Medical University, 789 Suzhou East Street, 830011, Urumqi, China;Operating Theatre, Affiliated Tumor Hospital of Xinjiang Medical University, 830011, Urumqi, China;State Key Laboratory of Pathogenesis, Prevention, and Treatment of High Incidence Diseases in Central Asia/Department of Gynecology, The First Affiliated Hospital of Xinjiang Medical University, 830054, Urumqi, China;The Second Department of Gynecology, Affiliated Tumor Hospital of Xinjiang Medical University, 830011, Urumqi, China;Xinjiang Key Laboratory of Oncology, Affiliated Tumor Hospital of Xinjiang Medical University, 830011, Urumqi, China;

关键词: CSCC;    mA;    METTL3;    lncRNA METTL4-2;    YTHDF1;   

DOI  :  10.1186/s12957-023-02907-z

 received in 2022-05-25, accepted in 2022-11-26,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundN6-Methyladenosine (m6A) and long non-coding RNAs (lncRNAs) are both crucial regulators in human cancer growth and metastasis. However, their regulation on cervical squamous cell carcinoma (CSCC) is largely unclear. The present study aimed to explore the role of m6A-associated lncRNAs in CSCC.MethodsWe screened the expression of methylation modification-related enzymes in CECC samples from TCGA. The qRT-PCR was used to detect METTL3 and lncRNA METTL4-2 expression. The biological activities of METTL3 in CSCC cells were evaluated by CCK-8, colony formation, transwell, wound healing, and xenograft tumor assays, respectively. The SRAMP tool was used to screen m6A modification sites of METTL4-2. Finally, the quantitative analysis of m6A modification was carried out by MeRIP.ResultsMETTL3 expression was upregulated in CSCC cells and tissues. Biological function and function loss analysis indicated that METTL3 promoted the migration and proliferation of CSCC cells. In addition, METTL3 promoted CSCC tumor growth in vivo. Mechanically, METTL3 installed the m6A modification and enhanced METTL4-2 transcript stability to increase its expression. Meanwhile, the m6A “reader” YTHDF1 recognized METTL4-2 installed by METTL3 and facilitated the translation of METTL4-2.ConclusionsIn conclusion, our study highlights the function and mechanism of METTL3-induced METTL4-2 in CSCC. These findings support that METTL3-stabilized METTL4-2 promoted CSCC progression via a m6A-dependent modality, which provides new insights into therapeutic strategies for CSCC.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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