Profiling of miRNAs and their interfering targets in peripheral blood mononuclear cells from patients with chronic myeloid leukaemia
IntroductionMicroRNAs may be implicated in the acquisition of drug resistance in chronic myeloid leukemia as they regulate the expression of not only BCR-ABL1 but also genes associated with the activation of drug transfer proteins or essential signaling pathways.MethodsTo understand the impact of sp...
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| Format: | Article |
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1173970/full |
| _version_ | 1797786735874146304 |
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| author | Sheng-Cheng Wu Shiue-Wei Lai Xin-Jie Lu Hsing-Fan Lai Yu-Guang Chen Po-Huang Chen Ching-Liang Ho Yi-Ying Wu Yi-Lin Chiu |
| author_facet | Sheng-Cheng Wu Shiue-Wei Lai Xin-Jie Lu Hsing-Fan Lai Yu-Guang Chen Po-Huang Chen Ching-Liang Ho Yi-Ying Wu Yi-Lin Chiu |
| author_sort | Sheng-Cheng Wu |
| collection | DOAJ |
| description | IntroductionMicroRNAs may be implicated in the acquisition of drug resistance in chronic myeloid leukemia as they regulate the expression of not only BCR-ABL1 but also genes associated with the activation of drug transfer proteins or essential signaling pathways.MethodsTo understand the impact of specifically expressed miRNAs in chronic myeloid leukemia and their target genes, we collected peripheral blood mononuclear cells (PBMC) from patients diagnosed with chronic myeloid leukemia (CML) and healthy donors to determine whole miRNA expression by small RNA sequencing and screened out 31 differentially expressed microRNAs (DE-miRNAs) with high expression. With the utilization of miRNA set enrichment analysis tools, we present here a comprehensive analysis of the relevance of DE-miRNAs to disease and biological function. Furthermore, the literature-based miRNA-target gene database was used to analyze the overall target genes of the DE-miRNAs and to define their associated biological responses. We further integrated DE-miRNA target genes to identify CML miRNA targeted gene signature singscore (CMTGSS) and used gene-set enrichment analysis (GSEA) to analyze the correlation between CMTGSS and Hallmark gene-sets in PBMC samples from clinical CML patients. Finally, the association of CMTGSS stratification with multiple CML cell lineage gene sets was validated in PBMC samples from CML patients using GSEA.ResultsAlthough individual miRNAs have been reported to have varying degrees of impact on CML, overall, our results show that abnormally upregulated miRNAs are associated with apoptosis and aberrantly downregulated miRNAs are associated with cell cycle. The clinical database shows that our defined DE-miRNAs are associated with the prognosis of CML patients. CMTGSS-based stratification analysis presented a tendency for miRNAs to affect cell differentiation in the blood microenvironment.ConclusionCollectively, this study defined differentially expressed miRNAs by miRNA sequencing from clinical samples and comprehensively analyzed the biological functions of the differential miRNAs in association with the target genes. The analysis of the enrichment of specific myeloid differentiated cells and immune cells also suggests the magnitude and potential targets of differentially expressed miRNAs in the clinical setting. It helps us to make links between the different results obtained from the multi-faceted studies to provide more potential research directions. |
| first_indexed | 2024-03-13T01:12:07Z |
| format | Article |
| id | doaj.art-d2c6f4b111f4447fa950742a528a2bad |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-13T01:12:07Z |
| publishDate | 2023-07-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-d2c6f4b111f4447fa950742a528a2bad2023-07-05T17:55:40ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-07-011310.3389/fonc.2023.11739701173970Profiling of miRNAs and their interfering targets in peripheral blood mononuclear cells from patients with chronic myeloid leukaemiaSheng-Cheng Wu0Shiue-Wei Lai1Xin-Jie Lu2Hsing-Fan Lai3Yu-Guang Chen4Po-Huang Chen5Ching-Liang Ho6Yi-Ying Wu7Yi-Lin Chiu8Division of Hematology and Oncology, Department of Internal Medicine, Tri-Service General Hospital Penghu Branch, Magong City, TaiwanDivision of Hematology and Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei City, TaiwanDepartment of Biochemistry, National Defense Medical Center, Taipei City, TaiwanDepartment of Biochemistry, National Defense Medical Center, Taipei City, TaiwanDivision of Hematology and Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei City, TaiwanDivision of Hematology and Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei City, TaiwanDivision of Hematology and Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei City, TaiwanDivision of Hematology and Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei City, TaiwanDepartment of Biochemistry, National Defense Medical Center, Taipei City, TaiwanIntroductionMicroRNAs may be implicated in the acquisition of drug resistance in chronic myeloid leukemia as they regulate the expression of not only BCR-ABL1 but also genes associated with the activation of drug transfer proteins or essential signaling pathways.MethodsTo understand the impact of specifically expressed miRNAs in chronic myeloid leukemia and their target genes, we collected peripheral blood mononuclear cells (PBMC) from patients diagnosed with chronic myeloid leukemia (CML) and healthy donors to determine whole miRNA expression by small RNA sequencing and screened out 31 differentially expressed microRNAs (DE-miRNAs) with high expression. With the utilization of miRNA set enrichment analysis tools, we present here a comprehensive analysis of the relevance of DE-miRNAs to disease and biological function. Furthermore, the literature-based miRNA-target gene database was used to analyze the overall target genes of the DE-miRNAs and to define their associated biological responses. We further integrated DE-miRNA target genes to identify CML miRNA targeted gene signature singscore (CMTGSS) and used gene-set enrichment analysis (GSEA) to analyze the correlation between CMTGSS and Hallmark gene-sets in PBMC samples from clinical CML patients. Finally, the association of CMTGSS stratification with multiple CML cell lineage gene sets was validated in PBMC samples from CML patients using GSEA.ResultsAlthough individual miRNAs have been reported to have varying degrees of impact on CML, overall, our results show that abnormally upregulated miRNAs are associated with apoptosis and aberrantly downregulated miRNAs are associated with cell cycle. The clinical database shows that our defined DE-miRNAs are associated with the prognosis of CML patients. CMTGSS-based stratification analysis presented a tendency for miRNAs to affect cell differentiation in the blood microenvironment.ConclusionCollectively, this study defined differentially expressed miRNAs by miRNA sequencing from clinical samples and comprehensively analyzed the biological functions of the differential miRNAs in association with the target genes. The analysis of the enrichment of specific myeloid differentiated cells and immune cells also suggests the magnitude and potential targets of differentially expressed miRNAs in the clinical setting. It helps us to make links between the different results obtained from the multi-faceted studies to provide more potential research directions.https://www.frontiersin.org/articles/10.3389/fonc.2023.1173970/fullchronic myeloid leukemiamicro RNAperipheral blood mononuclear cellapoptosishematopoietic stem cell differentiation |
| spellingShingle | Sheng-Cheng Wu Shiue-Wei Lai Xin-Jie Lu Hsing-Fan Lai Yu-Guang Chen Po-Huang Chen Ching-Liang Ho Yi-Ying Wu Yi-Lin Chiu Profiling of miRNAs and their interfering targets in peripheral blood mononuclear cells from patients with chronic myeloid leukaemia Frontiers in Oncology chronic myeloid leukemia micro RNA peripheral blood mononuclear cell apoptosis hematopoietic stem cell differentiation |
| title | Profiling of miRNAs and their interfering targets in peripheral blood mononuclear cells from patients with chronic myeloid leukaemia |
| title_full | Profiling of miRNAs and their interfering targets in peripheral blood mononuclear cells from patients with chronic myeloid leukaemia |
| title_fullStr | Profiling of miRNAs and their interfering targets in peripheral blood mononuclear cells from patients with chronic myeloid leukaemia |
| title_full_unstemmed | Profiling of miRNAs and their interfering targets in peripheral blood mononuclear cells from patients with chronic myeloid leukaemia |
| title_short | Profiling of miRNAs and their interfering targets in peripheral blood mononuclear cells from patients with chronic myeloid leukaemia |
| title_sort | profiling of mirnas and their interfering targets in peripheral blood mononuclear cells from patients with chronic myeloid leukaemia |
| topic | chronic myeloid leukemia micro RNA peripheral blood mononuclear cell apoptosis hematopoietic stem cell differentiation |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1173970/full |
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