Transcriptome-wide m6A methylome analysis uncovered the changes of m6A modification in oral pre-malignant cells compared with normal oral epithelial cells
As the most common post-transcriptional RNA modification, m6A methylation extensively regulates the structure and function of RNA. The dynamic and reversible modification of m6A is coordinated by m6A writers and erasers. m6A reader proteins recognize m6A modification on RNA, mediating different down...
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.939449/full |
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| author | Xun Chen Liutao Chen Liutao Chen Yuquan Tang Yi He Kuangwu Pan Linyu Yuan Weihong Xie Shangwu Chen Shangwu Chen Wei Zhao Dongsheng Yu |
| author_facet | Xun Chen Liutao Chen Liutao Chen Yuquan Tang Yi He Kuangwu Pan Linyu Yuan Weihong Xie Shangwu Chen Shangwu Chen Wei Zhao Dongsheng Yu |
| author_sort | Xun Chen |
| collection | DOAJ |
| description | As the most common post-transcriptional RNA modification, m6A methylation extensively regulates the structure and function of RNA. The dynamic and reversible modification of m6A is coordinated by m6A writers and erasers. m6A reader proteins recognize m6A modification on RNA, mediating different downstream biological functions. mRNA m6A modification and its corresponding regulators play an important role in cancers, but its characteristics in the precancerous stage are still unclear. In this study, we used oral precancerous DOK cells as a model to explore the characteristics of transcriptome-wide m6A modification and major m6A regulator expression in the precancerous stage compared with normal oral epithelial cell HOEC and oral cancer cell SCC-9 through MeRIP-seq and RT-PCR. Compared with HOEC cells, we found 1180 hyper-methylated and 1606 hypo-methylated m6A peaks and 354 differentially expressed mRNAs with differential m6A peaks in DOK cells. Although the change of m6A modification in DOK cells was less than that in SCC-9 cells, mRNAs with differential m6A in both cell lines were enriched into many identical GO terms and KEGG pathways. Among the 20 known m6A regulatory genes, FTO, ALKBH5, METTL3 and VIRMA were upregulated or downregulated in DOK cells, and the expression levels of 10 genes such as METTL14/16, FTO and IGF2BP2/3 were significantly changed in SCC-9 cells. Our data suggest that precancerous cells showed, to some extent, changes of m6A modification. Identifying some key m6A targets and corresponding regulators in precancerous stage may provide potential intervention targets for the prevention of cancer development through epigenetic modification in the future. |
| first_indexed | 2024-04-11T11:18:05Z |
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| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T11:18:05Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-2d1c1b269e9849658604762643b401a52022-12-22T04:27:09ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-09-011210.3389/fonc.2022.939449939449Transcriptome-wide m6A methylome analysis uncovered the changes of m6A modification in oral pre-malignant cells compared with normal oral epithelial cellsXun Chen0Liutao Chen1Liutao Chen2Yuquan Tang3Yi He4Kuangwu Pan5Linyu Yuan6Weihong Xie7Shangwu Chen8Shangwu Chen9Wei Zhao10Dongsheng Yu11Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, ChinaGuangdong Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory for Biocontrol, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou, ChinaHospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, ChinaHospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, ChinaHospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, ChinaHospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, ChinaHospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, ChinaGuangdong Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory for Biocontrol, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou, ChinaHospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, ChinaHospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, ChinaAs the most common post-transcriptional RNA modification, m6A methylation extensively regulates the structure and function of RNA. The dynamic and reversible modification of m6A is coordinated by m6A writers and erasers. m6A reader proteins recognize m6A modification on RNA, mediating different downstream biological functions. mRNA m6A modification and its corresponding regulators play an important role in cancers, but its characteristics in the precancerous stage are still unclear. In this study, we used oral precancerous DOK cells as a model to explore the characteristics of transcriptome-wide m6A modification and major m6A regulator expression in the precancerous stage compared with normal oral epithelial cell HOEC and oral cancer cell SCC-9 through MeRIP-seq and RT-PCR. Compared with HOEC cells, we found 1180 hyper-methylated and 1606 hypo-methylated m6A peaks and 354 differentially expressed mRNAs with differential m6A peaks in DOK cells. Although the change of m6A modification in DOK cells was less than that in SCC-9 cells, mRNAs with differential m6A in both cell lines were enriched into many identical GO terms and KEGG pathways. Among the 20 known m6A regulatory genes, FTO, ALKBH5, METTL3 and VIRMA were upregulated or downregulated in DOK cells, and the expression levels of 10 genes such as METTL14/16, FTO and IGF2BP2/3 were significantly changed in SCC-9 cells. Our data suggest that precancerous cells showed, to some extent, changes of m6A modification. Identifying some key m6A targets and corresponding regulators in precancerous stage may provide potential intervention targets for the prevention of cancer development through epigenetic modification in the future.https://www.frontiersin.org/articles/10.3389/fonc.2022.939449/fullm6A modificationm6A regulatory genesMeRIP sequencingprecancerous cellsdysplastic oral keratinocyte (DOK)human oral epithelial cell (HOEC) |
| spellingShingle | Xun Chen Liutao Chen Liutao Chen Yuquan Tang Yi He Kuangwu Pan Linyu Yuan Weihong Xie Shangwu Chen Shangwu Chen Wei Zhao Dongsheng Yu Transcriptome-wide m6A methylome analysis uncovered the changes of m6A modification in oral pre-malignant cells compared with normal oral epithelial cells Frontiers in Oncology m6A modification m6A regulatory genes MeRIP sequencing precancerous cells dysplastic oral keratinocyte (DOK) human oral epithelial cell (HOEC) |
| title | Transcriptome-wide m6A methylome analysis uncovered the changes of m6A modification in oral pre-malignant cells compared with normal oral epithelial cells |
| title_full | Transcriptome-wide m6A methylome analysis uncovered the changes of m6A modification in oral pre-malignant cells compared with normal oral epithelial cells |
| title_fullStr | Transcriptome-wide m6A methylome analysis uncovered the changes of m6A modification in oral pre-malignant cells compared with normal oral epithelial cells |
| title_full_unstemmed | Transcriptome-wide m6A methylome analysis uncovered the changes of m6A modification in oral pre-malignant cells compared with normal oral epithelial cells |
| title_short | Transcriptome-wide m6A methylome analysis uncovered the changes of m6A modification in oral pre-malignant cells compared with normal oral epithelial cells |
| title_sort | transcriptome wide m6a methylome analysis uncovered the changes of m6a modification in oral pre malignant cells compared with normal oral epithelial cells |
| topic | m6A modification m6A regulatory genes MeRIP sequencing precancerous cells dysplastic oral keratinocyte (DOK) human oral epithelial cell (HOEC) |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.939449/full |
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