Transcriptome-Wide Analysis of RNA N6-Methyladenosine Modification in Adriamycin-Resistant Acute Myeloid Leukemia Cells
Acute myeloid leukemia (AML) is one of the most aggressive hematopoietic malignancies. Patients still suffer from refractory/relapsed disease after anthracycline-based therapy, which leads to a poor prognosis. N6-Methyladenosine (m6A) is the most abundant post-transcriptional modification in eukaryo...
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.833694/full |
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| author | Shu Fang Shu Fang Bo Peng Yanan Wen Yanan Wen Jingjing Yang Jingjing Yang Hao Wang Hao Wang Ziwei Wang Kun Qian Kun Qian Yan Wei Yan Wei Yifan Jiao Yifan Jiao Chunji Gao Chunji Gao Liping Dou |
| author_facet | Shu Fang Shu Fang Bo Peng Yanan Wen Yanan Wen Jingjing Yang Jingjing Yang Hao Wang Hao Wang Ziwei Wang Kun Qian Kun Qian Yan Wei Yan Wei Yifan Jiao Yifan Jiao Chunji Gao Chunji Gao Liping Dou |
| author_sort | Shu Fang |
| collection | DOAJ |
| description | Acute myeloid leukemia (AML) is one of the most aggressive hematopoietic malignancies. Patients still suffer from refractory/relapsed disease after anthracycline-based therapy, which leads to a poor prognosis. N6-Methyladenosine (m6A) is the most abundant post-transcriptional modification in eukaryotes, the imbalance of which is reported to be associated with various pathological processes, including drug resistance. However, the relationship between m6A modification and drug resistance has not been well defined in AML. In this study, we analyzed the sequencing data of HL60 and its Adriamycin-resistant cell line HL60/ADR. We found a total of 40,550 m6A-methylated peaks, representing 15,640 genes in HL60, and 38,834 m6A-methylated peaks, representing 15,285 genes in HL60/ADR. KEGG pathway analysis showed that pathways were enriched in the FoxO signaling pathway, p53 signaling pathway, and Notch signaling pathway. MeRIP-seq results showed that the fold enrichment of the global m6A level in HL60/ADR was higher than that in HL60, and dot blot assay results indicated that the global m6A level was elevated in HL60/ADR cells compared with that in HL60 cells. Further analysis revealed that the expression level of METTL3 was elevated in HL60/ADR cells compared with that in HL60 cells. After a combined treatment of STM2457 (an inhibitor of METTL3) and Adriamycin, the proliferation of HL60/ADR was inhibited. Thus, we hypothesized that the abnormality of m6A modification played an important role in Adriamycin-resistant AML. |
| first_indexed | 2024-04-14T05:44:05Z |
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| id | doaj.art-9c6fad2788ed4dd7aa62a74fc0b042de |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-14T05:44:05Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-9c6fad2788ed4dd7aa62a74fc0b042de2022-12-22T02:09:20ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-04-011310.3389/fgene.2022.833694833694Transcriptome-Wide Analysis of RNA N6-Methyladenosine Modification in Adriamycin-Resistant Acute Myeloid Leukemia CellsShu Fang0Shu Fang1Bo Peng2Yanan Wen3Yanan Wen4Jingjing Yang5Jingjing Yang6Hao Wang7Hao Wang8Ziwei Wang9Kun Qian10Kun Qian11Yan Wei12Yan Wei13Yifan Jiao14Yifan Jiao15Chunji Gao16Chunji Gao17Liping Dou18School of Medicine, Nankai University, Tianjin, ChinaDepartment of Hematology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Hematology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Hematology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaMedical School of Chinese PLA, Beijing, ChinaDepartment of Hematology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaMedical School of Chinese PLA, Beijing, ChinaDepartment of Hematology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaMedical School of Chinese PLA, Beijing, ChinaDepartment of Hematology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaSchool of Medicine, Nankai University, Tianjin, ChinaDepartment of Hematology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Hematology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaMedical School of Chinese PLA, Beijing, ChinaDepartment of Hematology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaMedical School of Chinese PLA, Beijing, ChinaSchool of Medicine, Nankai University, Tianjin, ChinaDepartment of Hematology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Hematology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaAcute myeloid leukemia (AML) is one of the most aggressive hematopoietic malignancies. Patients still suffer from refractory/relapsed disease after anthracycline-based therapy, which leads to a poor prognosis. N6-Methyladenosine (m6A) is the most abundant post-transcriptional modification in eukaryotes, the imbalance of which is reported to be associated with various pathological processes, including drug resistance. However, the relationship between m6A modification and drug resistance has not been well defined in AML. In this study, we analyzed the sequencing data of HL60 and its Adriamycin-resistant cell line HL60/ADR. We found a total of 40,550 m6A-methylated peaks, representing 15,640 genes in HL60, and 38,834 m6A-methylated peaks, representing 15,285 genes in HL60/ADR. KEGG pathway analysis showed that pathways were enriched in the FoxO signaling pathway, p53 signaling pathway, and Notch signaling pathway. MeRIP-seq results showed that the fold enrichment of the global m6A level in HL60/ADR was higher than that in HL60, and dot blot assay results indicated that the global m6A level was elevated in HL60/ADR cells compared with that in HL60 cells. Further analysis revealed that the expression level of METTL3 was elevated in HL60/ADR cells compared with that in HL60 cells. After a combined treatment of STM2457 (an inhibitor of METTL3) and Adriamycin, the proliferation of HL60/ADR was inhibited. Thus, we hypothesized that the abnormality of m6A modification played an important role in Adriamycin-resistant AML.https://www.frontiersin.org/articles/10.3389/fgene.2022.833694/fullacute myeloid leukemiadrug resistanceN6-methyladenosinegene expressionMETTL3 |
| spellingShingle | Shu Fang Shu Fang Bo Peng Yanan Wen Yanan Wen Jingjing Yang Jingjing Yang Hao Wang Hao Wang Ziwei Wang Kun Qian Kun Qian Yan Wei Yan Wei Yifan Jiao Yifan Jiao Chunji Gao Chunji Gao Liping Dou Transcriptome-Wide Analysis of RNA N6-Methyladenosine Modification in Adriamycin-Resistant Acute Myeloid Leukemia Cells Frontiers in Genetics acute myeloid leukemia drug resistance N6-methyladenosine gene expression METTL3 |
| title | Transcriptome-Wide Analysis of RNA N6-Methyladenosine Modification in Adriamycin-Resistant Acute Myeloid Leukemia Cells |
| title_full | Transcriptome-Wide Analysis of RNA N6-Methyladenosine Modification in Adriamycin-Resistant Acute Myeloid Leukemia Cells |
| title_fullStr | Transcriptome-Wide Analysis of RNA N6-Methyladenosine Modification in Adriamycin-Resistant Acute Myeloid Leukemia Cells |
| title_full_unstemmed | Transcriptome-Wide Analysis of RNA N6-Methyladenosine Modification in Adriamycin-Resistant Acute Myeloid Leukemia Cells |
| title_short | Transcriptome-Wide Analysis of RNA N6-Methyladenosine Modification in Adriamycin-Resistant Acute Myeloid Leukemia Cells |
| title_sort | transcriptome wide analysis of rna n6 methyladenosine modification in adriamycin resistant acute myeloid leukemia cells |
| topic | acute myeloid leukemia drug resistance N6-methyladenosine gene expression METTL3 |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.833694/full |
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