Comprehensive Analysis of the Transcriptome-wide m6A Methylome in Lung Adenocarcinoma by MeRIP Sequencing.

Autor:	Mao W; Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, China., Yu Q; Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, China.; Medical Research Center, Southern University of Science and Technology Hospital, Shenzhen, China., Wang K; Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, China., Ma Q; Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, China., Zheng Y; Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, China., Zhang G; Nutrition Department, Southern University of Science and Technology Hospital, Shenzhen, China., Luo W; Department of Clinical Laboratory, Southern University of Science and Technology Hospital, Shenzhen, China., Wang N; Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, China., Wang Y; Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, China.; Department of Pharmacy, Southern University of Science and Technology Hospital, Shenzhen, China.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2022 Jul 11; Vol. 12, pp. 791332. Date of Electronic Publication: 2022 Jul 11 (Print Publication: 2022).
DOI:	10.3389/fonc.2022.791332
Abstrakt:	N6-methyladenosine (m6A) is the most abundant internal modification on eukaryotic mRNAs. There is increasing evidence that m6A plays a key role in tumor progression, so it is important to analyze m6A modifications within the transcriptome-wide in lung adenocarcinoma (LUAD). Three pairs of LUAD samples and tumor-adjacent normal tissues were obtained from the South University of Science and Technology Hospital. And then methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were used to identify differential m6A modifications between tumor and tumor-adjacent normal tissues. We identified 4041 aberrant m6A peaks, of which 1192 m6A peaks were upregulated and 2849 m6A peaks downregulated. It was found that genes with the dysregulated m6A peaks were enriched in the pathways in cancer, Rap1 signaling pathway, and insulin resistance. Additionally, 612 genes with abnormal regulation of m6A peaks and RNA expression were identified by combining MeRIP-seq and RNA-seq data. Through KEGG analysis, the 612 genes were enriched in cancer-related signaling pathways, such as the cGMP-PKG signaling pathway, and the Rap1 signaling pathway. What's more, GSEA enrichment analysis showed these genes were enriched in cell cycle phase transition, cell division, cellular response to DNA damage stimulus, and chromosome organization. To further explore the relationship between differential m6A modified genes and clinical parameters of LUAD patients, we searched The Cancer Genome Atlas (TCGA) and identified 2 genes (FCRL5 and GPRIN1) that were associated with the prognosis and diagnosis of LUAD patients. Furthermore, we found a positive correlation between GPRIN1 and m6A reader YTHDF1 in the GEPIA2 database. It was verified that YTHDF1 binds to GPRIN1 mRNA and regulates its expression. Our study results suggest that m6A modification plays important role in the progression and prognosis of LUAD and maybe a potential new therapeutic target for LUAD patients in the future. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Mao, Yu, Wang, Ma, Zheng, Zhang, Luo, Wang and Wang.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu