Deciphering the map of METTL14‐mediated lncRNA m6A modification at the transcriptome‐wide level in breast cancer

• Published in: Journal of clinical laboratory analysis Vol. 36; no. 12; pp. e24754 - n/a
• Main Authors: Yi, Dandan, Xu, Fazhan, Wang, Ru, Jiang, Chaoyu, Qin, Jiabo, Lee, YiHsuan, Shi, Xianbiao, Sang, Jianfeng
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.12.2022; John Wiley and Sons Inc
• Subjects: Antibodies; Biological Assay; Breast cancer; Breast Neoplasms - genetics; Data processing; Female; Gene expression; Genomes; Humans; long non‐coding RNA; Mammography; Membranes; MeRIP‐seq; Metastasis; Methylation; Methyltransferases - genetics; MicroRNAs; N6-methyladenosine; Non-coding RNA; Polymerase Chain Reaction; Proteins; Reagents; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; RNA‐seq; Statistical analysis; Transcriptome - genetics; Transcriptomes; Tumors; MeRIP-seq; breast cancer; N6-methyladenosine; long non-coding RNA; RNA-seq
• ISSN: 0887-8013; 1098-2825
• DOI: 10.1002/jcla.24754

Background Emerging studies have demonstrated the critical role of RNA m6A methylation in tumor progression, whereas lncRNA m6A modification profiles in breast cancer remain largely unknown. Our previous study has shown that METTL14 accelerates breast cancer migration and invasion in an m6A‐dependent manner, making it critical to analyze METTL14‐mediated m6A modification at a transcriptome‐wide scale in breast cancer. Methods Here, we performed MeRIP‐seq analysis in METTL14 overexpressed and control MDA‐MB‐231 cells. Conjoint analysis of MeRIP‐seq and RNA‐seq data was used to select lncRNAs with m6A methylation and differential expression. Finally, the screened lncRNA was verified by MeRIP‐PCR and its function was studied via transwell assay. Results Our results determined that high expression of METLL14 results in 3996 hypermethylation peaks from 3107 transcripts, and 4100 hypomethylation peaks from 2918 transcripts. Furthermore, conjoint analysis of MeRIP‐seq and RNA‐seq data identified 25 lncRNAs with discrepant methylation and simultaneously discrepant expression, among which the top 10 differentially expressed LncRNAs were AC026401.3, CYTOR, LINC01943, AC084125.2, FLJ20021, LINC00472, and NORAD, MALAT1, AL161431.1, and LINC01764. Moreover, over‐expressed METTL14 stimulated the m6A modification of AC084125.2, while decreasing its expression. Compared to adjacent tissues, AC084125.2 was lowly expressed in tumors and could be used as a biomarker in the diagnosis of breast cancer. Meanwhile, AC084125.2 inhibited the migration and invasion of cancer cells. Conclusion In conclusion, METTL14‐mediated m6A modification of lncRNAs, which might provide reference for future intervention in tumor progression. Mettl4‐mediated m6A modification is involved in breast cancer development.