An Integrated Regulatory Network Based on Comprehensive Analysis of mRNA Expression, Gene Methylation and Expression of Long Non-coding RNAs (lncRNAs) in Myelodysplastic Syndromes
Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by ineffective hematopoiesis, defective differentiation of hematopoietic precursors, and expansion of the abnormal clones. The prevalence of MDS has raised great concerns worldwide, but its pathogenetic mechanisms r...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-03-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2019.00200/full |
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| author | Xiaoli Zhao Xiaoli Zhao Hua Yin Nianyi Li Yu Zhu Wenyi Shen Sixuan Qian Guangsheng He Jianyong Li Xiaoqin Wang |
| author_facet | Xiaoli Zhao Xiaoli Zhao Hua Yin Nianyi Li Yu Zhu Wenyi Shen Sixuan Qian Guangsheng He Jianyong Li Xiaoqin Wang |
| author_sort | Xiaoli Zhao |
| collection | DOAJ |
| description | Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by ineffective hematopoiesis, defective differentiation of hematopoietic precursors, and expansion of the abnormal clones. The prevalence of MDS has raised great concerns worldwide, but its pathogenetic mechanisms remain elusive. To provide insights on novel biomarkers for the diagnosis and therapy of MDS, we performed high-throughput genome-wide mRNA expression profiling, DNA methylation analysis, and long non-coding RNAs (lncRNA) analysis on bone marrows from four MDS patients and four age-matched healthy controls. We identified 1,937 differentially expressed genes (DEGs), 515 methylated genes, and 214 lncRNA that showed statistically significant differences. As the most significant module-related DEGs, TCL1A, PTGS2, and MME were revealed to be enriched in regulation of cell differentiation and cell death pathways. In addition, the GeneGo pathway maps identified by top DEGs were shown to converge on cancer, immunoregulation, apoptosis and regulation of actin cytoskeleton, most of which are known contributors in MDS etiology and pathogenesis. Notably, as potential biomarkers for diagnosis of MDS, four specific genes (ABAT, FADD, DAPP1, and SMPD3) were further subjected to detailed pathway analysis. Our integrative analysis on mRNA expression, gene methylation and lncRNAs profiling facilitates further understanding of the pathogenesis of MDS, and may promote the diagnosis and novel therapeutics for this disease. |
| first_indexed | 2024-12-10T05:11:50Z |
| format | Article |
| id | doaj.art-ae5a67706eb14df9b60c48502a03b794 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-10T05:11:50Z |
| publishDate | 2019-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-ae5a67706eb14df9b60c48502a03b7942022-12-22T02:01:05ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-03-01910.3389/fonc.2019.00200429228An Integrated Regulatory Network Based on Comprehensive Analysis of mRNA Expression, Gene Methylation and Expression of Long Non-coding RNAs (lncRNAs) in Myelodysplastic SyndromesXiaoli Zhao0Xiaoli Zhao1Hua Yin2Nianyi Li3Yu Zhu4Wenyi Shen5Sixuan Qian6Guangsheng He7Jianyong Li8Xiaoqin Wang9Key Laboratory of Hematology, Department of Hematology, Collaborative Innovation Center for Cancer Personalized Medicine, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Haematology, Huashan Hospital, Fudan University, Shanghai, ChinaKey Laboratory of Hematology, Department of Hematology, Collaborative Innovation Center for Cancer Personalized Medicine, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Haematology, Huashan Hospital, Fudan University, Shanghai, ChinaKey Laboratory of Hematology, Department of Hematology, Collaborative Innovation Center for Cancer Personalized Medicine, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing Medical University, Nanjing, ChinaKey Laboratory of Hematology, Department of Hematology, Collaborative Innovation Center for Cancer Personalized Medicine, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing Medical University, Nanjing, ChinaKey Laboratory of Hematology, Department of Hematology, Collaborative Innovation Center for Cancer Personalized Medicine, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing Medical University, Nanjing, ChinaKey Laboratory of Hematology, Department of Hematology, Collaborative Innovation Center for Cancer Personalized Medicine, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing Medical University, Nanjing, ChinaKey Laboratory of Hematology, Department of Hematology, Collaborative Innovation Center for Cancer Personalized Medicine, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Haematology, Huashan Hospital, Fudan University, Shanghai, ChinaMyelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by ineffective hematopoiesis, defective differentiation of hematopoietic precursors, and expansion of the abnormal clones. The prevalence of MDS has raised great concerns worldwide, but its pathogenetic mechanisms remain elusive. To provide insights on novel biomarkers for the diagnosis and therapy of MDS, we performed high-throughput genome-wide mRNA expression profiling, DNA methylation analysis, and long non-coding RNAs (lncRNA) analysis on bone marrows from four MDS patients and four age-matched healthy controls. We identified 1,937 differentially expressed genes (DEGs), 515 methylated genes, and 214 lncRNA that showed statistically significant differences. As the most significant module-related DEGs, TCL1A, PTGS2, and MME were revealed to be enriched in regulation of cell differentiation and cell death pathways. In addition, the GeneGo pathway maps identified by top DEGs were shown to converge on cancer, immunoregulation, apoptosis and regulation of actin cytoskeleton, most of which are known contributors in MDS etiology and pathogenesis. Notably, as potential biomarkers for diagnosis of MDS, four specific genes (ABAT, FADD, DAPP1, and SMPD3) were further subjected to detailed pathway analysis. Our integrative analysis on mRNA expression, gene methylation and lncRNAs profiling facilitates further understanding of the pathogenesis of MDS, and may promote the diagnosis and novel therapeutics for this disease.https://www.frontiersin.org/article/10.3389/fonc.2019.00200/fullmyelodysplastic syndromesdifferentially expressed genesmethylated genesmicroRNAslncRNAsregulatory network |
| spellingShingle | Xiaoli Zhao Xiaoli Zhao Hua Yin Nianyi Li Yu Zhu Wenyi Shen Sixuan Qian Guangsheng He Jianyong Li Xiaoqin Wang An Integrated Regulatory Network Based on Comprehensive Analysis of mRNA Expression, Gene Methylation and Expression of Long Non-coding RNAs (lncRNAs) in Myelodysplastic Syndromes Frontiers in Oncology myelodysplastic syndromes differentially expressed genes methylated genes microRNAs lncRNAs regulatory network |
| title | An Integrated Regulatory Network Based on Comprehensive Analysis of mRNA Expression, Gene Methylation and Expression of Long Non-coding RNAs (lncRNAs) in Myelodysplastic Syndromes |
| title_full | An Integrated Regulatory Network Based on Comprehensive Analysis of mRNA Expression, Gene Methylation and Expression of Long Non-coding RNAs (lncRNAs) in Myelodysplastic Syndromes |
| title_fullStr | An Integrated Regulatory Network Based on Comprehensive Analysis of mRNA Expression, Gene Methylation and Expression of Long Non-coding RNAs (lncRNAs) in Myelodysplastic Syndromes |
| title_full_unstemmed | An Integrated Regulatory Network Based on Comprehensive Analysis of mRNA Expression, Gene Methylation and Expression of Long Non-coding RNAs (lncRNAs) in Myelodysplastic Syndromes |
| title_short | An Integrated Regulatory Network Based on Comprehensive Analysis of mRNA Expression, Gene Methylation and Expression of Long Non-coding RNAs (lncRNAs) in Myelodysplastic Syndromes |
| title_sort | integrated regulatory network based on comprehensive analysis of mrna expression gene methylation and expression of long non coding rnas lncrnas in myelodysplastic syndromes |
| topic | myelodysplastic syndromes differentially expressed genes methylated genes microRNAs lncRNAs regulatory network |
| url | https://www.frontiersin.org/article/10.3389/fonc.2019.00200/full |
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