Exogenous Janus Kinase 617 Codon Influences Small Noncoding RNAs and Gene Expression in Ba/F3 Cells
Myeloproliferative neoplasms (MPNs) are blood cancers caused by mutations that originate from hematopoietic stem cells. More than 50%–90% of MPN patients had a dominant negative valine (V) to phenylalanine (F) mutation at the Janus kinase 617 codon (JAK2V617F) within the Janus kinase (JAK)-signal tr...
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Wolters Kluwer Medknow Publications
2024-12-01
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| Series: | Journal of Physiological Investigation |
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| Online Access: | https://journals.lww.com/cjop/fulltext/2024/67060/exogenous_janus_kinase_617_codon_influences_small.6.aspx |
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| author | Yi-Yang Chen Ying-Hsuan Wang Chih-Cheng Chen Cih-En Huang Chia-Chen Hsu Shu-Huei Hsiao Yu-Wei Leu |
| author_facet | Yi-Yang Chen Ying-Hsuan Wang Chih-Cheng Chen Cih-En Huang Chia-Chen Hsu Shu-Huei Hsiao Yu-Wei Leu |
| author_sort | Yi-Yang Chen |
| collection | DOAJ |
| description | Myeloproliferative neoplasms (MPNs) are blood cancers caused by mutations that originate from hematopoietic stem cells. More than 50%–90% of MPN patients had a dominant negative valine (V) to phenylalanine (F) mutation at the Janus kinase 617 codon (JAK2V617F) within the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway; however, this mutation was also found in a high percentage of the general population, its penetrance varied, and its onset was shown to be polygenic. Consequently, it is still unknown what molecular mechanism underlies the MPN transformation produced by JAK2V617F. Patients with MPN have been shown to have dysregulation of noncoding RNAs, such as microRNA (miRNA) and PIWI-interacting RNA (piRNA), although there is not any concrete proof that JAK2V617F alone is responsible for the aberrant regulation of miRNA and piRNA. Human wild type versus V617F-mutated JAK2 are expressed in mouse Ba/F3 cells, and the expressed small and total RNAs were subjected to next generation sequencing analysis to determine the direct induction. Differentially expressed miRNAs, gene expression, and transcript and gene variations were found between exogenously expressed JAK2 and JAK2V617F in Ba/F3 cells. The differently expressed variations contained enriched transposable elements and piRNAs, indicating a rearranged epigenome. The results of the pathway analysis show that the transformation that self-validated the chosen sequencing target genes is impacted by the JAK-STAT pathway. The induction route is functionally conserved, according to exogenously produced miRNA and gene expression. These results may clarify how the JAK2V617F induces transformation. |
| format | Article |
| id | doaj-art-f17887801fcf47b6a0a4f56ffba89293 |
| institution | Kabale University |
| issn | 2950-6344 2950-6352 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Journal of Physiological Investigation |
| spelling | doaj-art-f17887801fcf47b6a0a4f56ffba892932025-01-16T10:31:11ZengWolters Kluwer Medknow PublicationsJournal of Physiological Investigation2950-63442950-63522024-12-0167634435410.4103/ejpi.EJPI-D-24-00047Exogenous Janus Kinase 617 Codon Influences Small Noncoding RNAs and Gene Expression in Ba/F3 CellsYi-Yang ChenYing-Hsuan WangChih-Cheng ChenCih-En HuangChia-Chen HsuShu-Huei HsiaoYu-Wei LeuMyeloproliferative neoplasms (MPNs) are blood cancers caused by mutations that originate from hematopoietic stem cells. More than 50%–90% of MPN patients had a dominant negative valine (V) to phenylalanine (F) mutation at the Janus kinase 617 codon (JAK2V617F) within the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway; however, this mutation was also found in a high percentage of the general population, its penetrance varied, and its onset was shown to be polygenic. Consequently, it is still unknown what molecular mechanism underlies the MPN transformation produced by JAK2V617F. Patients with MPN have been shown to have dysregulation of noncoding RNAs, such as microRNA (miRNA) and PIWI-interacting RNA (piRNA), although there is not any concrete proof that JAK2V617F alone is responsible for the aberrant regulation of miRNA and piRNA. Human wild type versus V617F-mutated JAK2 are expressed in mouse Ba/F3 cells, and the expressed small and total RNAs were subjected to next generation sequencing analysis to determine the direct induction. Differentially expressed miRNAs, gene expression, and transcript and gene variations were found between exogenously expressed JAK2 and JAK2V617F in Ba/F3 cells. The differently expressed variations contained enriched transposable elements and piRNAs, indicating a rearranged epigenome. The results of the pathway analysis show that the transformation that self-validated the chosen sequencing target genes is impacted by the JAK-STAT pathway. The induction route is functionally conserved, according to exogenously produced miRNA and gene expression. These results may clarify how the JAK2V617F induces transformation.https://journals.lww.com/cjop/fulltext/2024/67060/exogenous_janus_kinase_617_codon_influences_small.6.aspxepigeneticsmicrornamyeloproliferative neoplasmspiwi-interacting rnav617f mutation |
| spellingShingle | Yi-Yang Chen Ying-Hsuan Wang Chih-Cheng Chen Cih-En Huang Chia-Chen Hsu Shu-Huei Hsiao Yu-Wei Leu Exogenous Janus Kinase 617 Codon Influences Small Noncoding RNAs and Gene Expression in Ba/F3 Cells Journal of Physiological Investigation epigenetics microrna myeloproliferative neoplasms piwi-interacting rna v617f mutation |
| title | Exogenous Janus Kinase 617 Codon Influences Small Noncoding RNAs and Gene Expression in Ba/F3 Cells |
| title_full | Exogenous Janus Kinase 617 Codon Influences Small Noncoding RNAs and Gene Expression in Ba/F3 Cells |
| title_fullStr | Exogenous Janus Kinase 617 Codon Influences Small Noncoding RNAs and Gene Expression in Ba/F3 Cells |
| title_full_unstemmed | Exogenous Janus Kinase 617 Codon Influences Small Noncoding RNAs and Gene Expression in Ba/F3 Cells |
| title_short | Exogenous Janus Kinase 617 Codon Influences Small Noncoding RNAs and Gene Expression in Ba/F3 Cells |
| title_sort | exogenous janus kinase 617 codon influences small noncoding rnas and gene expression in ba f3 cells |
| topic | epigenetics microrna myeloproliferative neoplasms piwi-interacting rna v617f mutation |
| url | https://journals.lww.com/cjop/fulltext/2024/67060/exogenous_janus_kinase_617_codon_influences_small.6.aspx |
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