The M6A Methyltransferase METTL3 drives thyroid cancer progression and lymph node metastasis by targeting LINC00894

Abstract

Abstract Background：Long non-coding RNAs (lncRNAs) are significant contributors to various human malignancies. The aberrant expression of lncRNA LINC00894 has been referred to in various human malignancies. Consequently, our aim is to illustrate the role of LINC00894 and its underlying mechanism in the development of papillary thyroid carcinoma (PTC). Method：Bioinformatics analysis of differentially expressed RNA from TCGA and GEO datasets and selected the target lncRNA LINC00894.The analysis of SRAMP found that there are abundant M6A methylation sites in LINC00894. And further analysis from StarBase, GEPIA, and TCGA datasets to find related differentially expressed genes METTL3. The Colony formation and CCK8 assay confirmed the relationship between LINC00894, METTL3, and the proliferative capacity of PTC cells. The analysis of AnnoLnc2, Starbase datasets, and meRIP-PCR, qRT-PCR confirmed the influence of Mettl3-mediated modification of M6A on LINC00894. The study employed KEGG enrichment analysis as well as Western blotting to investigate the impact of LINC00894 on the expression of proteins related to the Hippo signaling pathway. Results：LINC00894 hypoexpression was detected in PTC tissues and cells and even lower in PTC with lymphatic metastasis. LINC00894 inhibits the lymphangiogenesis of vascular endothelial cells and the proliferation of cancer cells. METTL3 enhances PTC progression by upregulating LINC00894, which relies on enhancing the LINC00894 mRNA stability through the M6A-YTHDC2-dependent pathway.LINC00894 may inhibit PTC malignant phenotypes through the Hippo signaling pathway. Conclusion： The METTL3-YTHDC2 axis stabilizes LINC00894 mRNA in an M6A-dependent manner and subsequently inhibits tumor malignancy through the Hippo signaling pathway.