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

BACKGROUND

N-Methyladenosine (mA) 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 mA-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 mA modification sites of METTL4-2. Finally, the quantitative analysis of mA 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 mA modification and enhanced METTL4-2 transcript stability to increase its expression. Meanwhile, the mA "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 mA-dependent modality, which provides new insights into therapeutic strategies for CSCC.