Joint analysis of lncRNA m6A methylome and lncRNA/mRNA expression profiles in gastric cancer - PubMed (original) (raw)

Joint analysis of lncRNA m6A methylome and lncRNA/mRNA expression profiles in gastric cancer

Zhi Lv et al. Cancer Cell Int. 2020.

Abstract

Background: N 6-methyladenosine (m6A) modification might be closely associated with the genesis and development of gastric cancer (GC). Currently, the evidence established by high-throughput assay for GC-related m6A patterns based on long non-coding RNAs (lncRNAs) remains limited. Here, a joint analysis of lncRNA m6A methylome and lncRNA/mRNA expression profiles in GC was performed to explore the regulatory roles of m6A modification in lncRNAs.

Methods: Three subjects with primary GC were enrolled in our study and paired sample was randomly selected from GC tissue and adjacent normal tissue for each case. Methylated RNA Immunoprecipitation NextGeneration Sequencing (MeRIP-Seq) and Microarray Gene Expression Profiling was subsequently performed. Then co-expression analysis and gene enrichment analysis were successively conducted.

Results: After data analysis, we identified 191 differentially m6A-methylated lncRNAs, 240 differentially expressed lncRNAs and 229 differentially expressed mRNAs in GC. Furthermore, four differentially m6A-methylated and expressed lncRNAs (dme-lncRNAs) were discovered including RASAL2-AS1, LINC00910, SNHG7 and LINC01105. Their potential target genes were explored by co-expression analysis. And gene enrichment analysis suggested that they might influence the cellular processes and biological behaviors involved in mitosis and cell cycle. The potential impacts of these targets on GC cells were further validated by CCLE database and literature review.

Conclusions: Four novel dme-lncRNAs were identified in GC, which might exert regulatory roles on GC cell proliferation. The present study would provide clues for the lncRNA m6A methylation-based research on GC epigenetic etiology and pathogenesis.

Keywords: Expression profile; Gastric cancer; LncRNA; Methylome profile; m6A.

© The Author(s) 2020.

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Conflict of interest statement

Competing interestsThe authors declare that they have no competing interests.

Figures

Fig. 1

Fig. 1

The overall features of lncRNA m6A methylome in GC. a the quantitative data of RNA transcripts in MeRIP and m6A-methylated lncRNAs; b the peak width distribution of lncRNA m6A-methylated sites in sequencing; c the source distribution of m6A-methylated lncRNAs

Fig. 2

Fig. 2

The heat map of expression levels for differentially expressed lncRNAs and mRNAs in GC

Fig. 3

Fig. 3

The Venn diagram of differentially m6A-methylated lncRNAs and differentially expressed lncRNAs in GC

Fig. 4

Fig. 4

The co-expression network of dme-lncRNAs and differentially co-expressed mRNAs in GC

Fig. 5

Fig. 5

The prediction of top 10 expression sites in the enrichment analysis of differentially co-expressed genes in GC. FE fold enrichment

Fig. 6

Fig. 6

The GO-term enrichment analysis of differentially co-expressed genes in GC. Top 10 items were selected for each term. a cellular component; b molecular function; c biological process

Fig. 7

Fig. 7

The pathway analysis of differentially co-expressed genes in GC. Top 10 items were selected

Fig. 8

Fig. 8

The differences in mRNA expression levels of selected differentially co-expressed genes in GC cell lines grouped by differentiation

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References

    1. Meyer KD, Saletore Y, Zumbo P, Elemento O, Mason CE, Jaffrey SR. Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons. Cell. 2012;149(7):1635–1646. doi: 10.1016/j.cell.2012.05.003. - DOI - PMC - PubMed
    1. Dominissini D, Moshitch-Moshkovitz S, Schwartz S, Salmon-Divon M, Ungar L, Osenberg S, et al. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature. 2012;485(7397):201–206. doi: 10.1038/nature11112. - DOI - PubMed
    1. Fazi F, Fatica A. Interplay between N(6)-methyladenosine (m(6)A) and non-coding RNAs in cell development and cancer. Front Cell Dev Biol. 2019;7:116. doi: 10.3389/fcell.2019.00116. - DOI - PMC - PubMed
    1. Zhou C, Molinie B, Daneshvar K, Pondick JV, Wang J, Van Wittenberghe N, et al. Genome-Wide Maps of m6A circRNAs identify widespread and cell-type-specific methylation patterns that are distinct from mRNAs. Cell Rep. 2017;20(9):2262–2276. doi: 10.1016/j.celrep.2017.08.027. - DOI - PMC - PubMed
    1. Ge L, Zhang N, Chen Z, Song J, Wu Y, Li Z, et al. Level of N6-methyladenosine in peripheral blood RNA: a novel predictive biomarker for gastric cancer. Clin Chem. 2020;66(2):342–351. doi: 10.1093/clinchem/hvz004. - DOI - PubMed

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