Exogenous Janus Kinase 617 Codon Influences Small Noncoding RNAs and Gene Expression in Ba/F3 Cells.

Autor:	Chen YY; Division of Hematology and Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan., Wang YH; Division of Hematology and Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan.; College of Medicine, Chang Gung University, Taoyuan, Taiwan., Chen CC; Division of Hematology and Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan.; College of Medicine, Chang Gung University, Taoyuan, Taiwan., Huang CE; Division of Hematology and Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan.; College of Medicine, Chang Gung University, Taoyuan, Taiwan., Hsu CC; Division of Hematology and Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan., Hsiao SH; Department of Biomedical Sciences, Institute of Molecular Biology and Institute of Biomedical Sciences, National Chung Cheng University, Chiayi, Taiwan., Leu YW; Department of Biomedical Sciences, Institute of Molecular Biology and Institute of Biomedical Sciences, National Chung Cheng University, Chiayi, Taiwan.
Jazyk:	angličtina
Zdroj:	Journal of physiological investigation [J Physiol Investig] 2024 Nov 01; Vol. 67 (6), pp. 344-354. Date of Electronic Publication: 2024 Sep 26.
DOI:	10.4103/ejpi.EJPI-D-24-00047
Abstrakt:	Abstract: 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. (Copyright © 2024 Journal of Physiological Investigation.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu