Dysregulation of transposable elements and PIWI-interacting RNAs in myelodysplastic neoplasms
Abstract Background Myelodysplastic neoplasms (MDS) are heterogeneous hematopoietic disorders characterized by ineffective hematopoiesis and genome instability. Mobilization of transposable elements (TEs) is an important source of genome instability leading to oncogenesis, whereas small PIWI-interac...
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2025-01-01
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| Online Access: | https://doi.org/10.1186/s40364-025-00725-x |
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| author | Zdenek Krejcik David Kundrat Jiri Klema Andrea Hrustincova Iva Trsova Monika Belickova Jaroslav Cermak Anna Jonasova Jiri Dostal Michaela Dostalova Merkerova |
| author_facet | Zdenek Krejcik David Kundrat Jiri Klema Andrea Hrustincova Iva Trsova Monika Belickova Jaroslav Cermak Anna Jonasova Jiri Dostal Michaela Dostalova Merkerova |
| author_sort | Zdenek Krejcik |
| collection | DOAJ |
| description | Abstract Background Myelodysplastic neoplasms (MDS) are heterogeneous hematopoietic disorders characterized by ineffective hematopoiesis and genome instability. Mobilization of transposable elements (TEs) is an important source of genome instability leading to oncogenesis, whereas small PIWI-interacting RNAs (piRNAs) act as cellular suppressors of TEs. However, the roles of TEs and piRNAs in MDS remain unclear. Methods In this study, we examined TE and piRNA expression through parallel RNA and small RNA sequencing of CD34+ hematopoietic stem cells from MDS patients. Results Comparative analysis of TE and piRNA expression between MDS and control samples revealed several significantly dysregulated molecules. However, significant differences were observed between lower-risk MDS (LR-MDS) and higher-risk MDS (HR-MDS) samples. In HR-MDS, we found an inverse correlation between decreased TE levels and increased piRNA expression and these TE and piRNA levels were significantly associated with patient outcomes. Importantly, the upregulation of PIWIL2, which encodes a key factor in the piRNA pathway, independently predicted poor prognosis in MDS patients, underscoring its potential as a valuable disease marker. Furthermore, pathway analysis of RNA sequencing data revealed that dysregulation of the TE‒piRNA axis is linked to the suppression of processes related to energy metabolism, the cell cycle, and the immune response, suggesting that these disruptions significantly affect cellular activity. Conclusions Our findings demonstrate the parallel dysregulation of TEs and piRNAs in HR-MDS patients, highlighting their potential role in MDS progression and indicating that the PIWIL2 level is a promising molecular marker for prognosis. Graphical Abstract |
| format | Article |
| id | doaj-art-006f1940df3d499880cb7679bcf30112 |
| institution | Kabale University |
| issn | 2050-7771 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Biomarker Research |
| spelling | doaj-art-006f1940df3d499880cb7679bcf301122025-01-26T12:45:40ZengBMCBiomarker Research2050-77712025-01-0113111710.1186/s40364-025-00725-xDysregulation of transposable elements and PIWI-interacting RNAs in myelodysplastic neoplasmsZdenek Krejcik0David Kundrat1Jiri Klema2Andrea Hrustincova3Iva Trsova4Monika Belickova5Jaroslav Cermak6Anna Jonasova7Jiri Dostal8Michaela Dostalova Merkerova9Department of Genomics, Institute of Hematology and Blood TransfusionDepartment of Genomics, Institute of Hematology and Blood TransfusionDepartment of Computer Science, Faculty of Electrical Engineering, Czech Technical University in PragueDepartment of Genomics, Institute of Hematology and Blood TransfusionDepartment of Genomics, Institute of Hematology and Blood TransfusionDepartment of Genomics, Institute of Hematology and Blood TransfusionLaboratory of Anemias, Institute of Hematology and Blood TransfusionFirst Department of Medicine, General University HospitalDepartment of Biochemistry, Institute of Organic Chemistry and Biochemistry, Czech Academy of SciencesDepartment of Genomics, Institute of Hematology and Blood TransfusionAbstract Background Myelodysplastic neoplasms (MDS) are heterogeneous hematopoietic disorders characterized by ineffective hematopoiesis and genome instability. Mobilization of transposable elements (TEs) is an important source of genome instability leading to oncogenesis, whereas small PIWI-interacting RNAs (piRNAs) act as cellular suppressors of TEs. However, the roles of TEs and piRNAs in MDS remain unclear. Methods In this study, we examined TE and piRNA expression through parallel RNA and small RNA sequencing of CD34+ hematopoietic stem cells from MDS patients. Results Comparative analysis of TE and piRNA expression between MDS and control samples revealed several significantly dysregulated molecules. However, significant differences were observed between lower-risk MDS (LR-MDS) and higher-risk MDS (HR-MDS) samples. In HR-MDS, we found an inverse correlation between decreased TE levels and increased piRNA expression and these TE and piRNA levels were significantly associated with patient outcomes. Importantly, the upregulation of PIWIL2, which encodes a key factor in the piRNA pathway, independently predicted poor prognosis in MDS patients, underscoring its potential as a valuable disease marker. Furthermore, pathway analysis of RNA sequencing data revealed that dysregulation of the TE‒piRNA axis is linked to the suppression of processes related to energy metabolism, the cell cycle, and the immune response, suggesting that these disruptions significantly affect cellular activity. Conclusions Our findings demonstrate the parallel dysregulation of TEs and piRNAs in HR-MDS patients, highlighting their potential role in MDS progression and indicating that the PIWIL2 level is a promising molecular marker for prognosis. Graphical Abstracthttps://doi.org/10.1186/s40364-025-00725-xMyelodysplastic neoplasmsTransposable elementspiRNANext-generation sequencingBiomarkersBioinformatics |
| spellingShingle | Zdenek Krejcik David Kundrat Jiri Klema Andrea Hrustincova Iva Trsova Monika Belickova Jaroslav Cermak Anna Jonasova Jiri Dostal Michaela Dostalova Merkerova Dysregulation of transposable elements and PIWI-interacting RNAs in myelodysplastic neoplasms Biomarker Research Myelodysplastic neoplasms Transposable elements piRNA Next-generation sequencing Biomarkers Bioinformatics |
| title | Dysregulation of transposable elements and PIWI-interacting RNAs in myelodysplastic neoplasms |
| title_full | Dysregulation of transposable elements and PIWI-interacting RNAs in myelodysplastic neoplasms |
| title_fullStr | Dysregulation of transposable elements and PIWI-interacting RNAs in myelodysplastic neoplasms |
| title_full_unstemmed | Dysregulation of transposable elements and PIWI-interacting RNAs in myelodysplastic neoplasms |
| title_short | Dysregulation of transposable elements and PIWI-interacting RNAs in myelodysplastic neoplasms |
| title_sort | dysregulation of transposable elements and piwi interacting rnas in myelodysplastic neoplasms |
| topic | Myelodysplastic neoplasms Transposable elements piRNA Next-generation sequencing Biomarkers Bioinformatics |
| url | https://doi.org/10.1186/s40364-025-00725-x |
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