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

• Published in: World journal of surgical oncology Vol. 21; no. 1; pp. 1 - 25
• Main Authors: Shen, Guqun, Li, Fen, Wang, Yan, Huang, Yongmei, Aizezi, Gulibiya, Yuan, Jinrui, Ma, Cailing, Lin, Chen
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 30-01-2023; BioMed Central; BMC
• Subjects: Analysis; Cancer; Care and treatment; Cell proliferation; Cells; Cervical cancer; Cholecystokinin; CSCC; Development and progression; Gene expression; Human papillomavirus; lncRNA METTL4-2; m6A; Medical screening; Metastases; Metastasis; Methylation; Methyltransferases; METTL3; N6-methyladenosine; Non-coding RNA; Prevention; Proteins; Reagents; Risk factors; RNA modification; Squamous cell carcinoma; Tumors; Wound healing; Xenografts; Xenotransplantation; YTHDF1; China; United Kingdom > UK; United States > US; Japan
• ISSN: 1477-7819; 1477-7819
• DOI: 10.1186/s12957-023-02907-z

Background N.sup.6-Methyladenosine (m.sup.6A) 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 m.sup.6A-associated lncRNAs in CSCC. Methods We 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 m.sup.6A modification sites of METTL4-2. Finally, the quantitative analysis of m.sup.6A modification was carried out by MeRIP. Results METTL3 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 m.sup.6A modification and enhanced METTL4-2 transcript stability to increase its expression. Meanwhile, the m.sup.6A "reader" YTHDF1 recognized METTL4-2 installed by METTL3 and facilitated the translation of METTL4-2. Conclusions In 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 m.sup.6A-dependent modality, which provides new insights into therapeutic strategies for CSCC. Keywords: CSCC, m.sup.6A, METTL3, lncRNA METTL4-2, YTHDF1