The Long Noncoding RNA MEG3 and its Target miR-147 Regulate JAK/STAT Pathway in Advanced Chronic Myeloid Leukemia
Autor: | Yuxia Pan, Lin Yang, Zi-ye Li, Jianmin Luo, Xiao-Jun Liu, Xingzhe Wang |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
Adult
Male STAT3 Transcription Factor 0301 basic medicine Adolescent Mice Nude lcsh:Medicine Biology General Biochemistry Genetics and Molecular Biology Young Adult 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Leukemia Myelogenous Chronic BCR-ABL Positive Chidamide hemic and lymphatic diseases STAT5 Transcription Factor Animals Humans Child STAT5 Aged MEG3 lcsh:R5-920 lcsh:R RNA Myeloid leukemia JAK-STAT signaling pathway General Medicine Methylation Janus Kinase 2 Middle Aged Long non-coding RNA MicroRNAs 030104 developmental biology chemistry 030220 oncology & carcinogenesis embryonic structures biology.protein Cancer research Female RNA Long Noncoding Corrigendum lcsh:Medicine (General) Signal Transduction |
Zdroj: | EBioMedicine, Vol 34, Iss, Pp 61-75 (2018) EBioMedicine |
ISSN: | 2352-3964 |
Popis: | Background: Long non-coding (lnc) RNAs plays an important role in chronic myeloid leukemia (CML). In this study, we aimed to uncover the mechanism of the lncRNA maternally expressed 3 (MEG3) and its target microRNA-147 (miR-147) in CML. Methods: Sixty CML patients and 10 healthy donors were included in the study. The methylation of MEG3 and miR-147 promoter was determined by methylation-specific PCR. The relationship of MEG3 and miR-147 was explored by luciferase assay. The interactions of proteins were studied by RNA pull-down assay, RNA immunoprecipitation and co-immunoprecipitation. Findings: Patients in accelerated phase CML (CML-AP) and blast phase CML (CML-BP) showed lower expressions of MEG3 and miR-147 and higher expressions of DNMT1, DNMT3B, MBD2, MECP2 and HDAC1 compared to the controls. These patients also showed a higher degree of methylation of MEG3 and miR-147 while there was a reduction after chidamide treatment. Furthermore, the overexpression of MEG3 and miR-147 inhibited cell proliferation both in vivo and in vitro, promoted apoptosis and decreased the expressions of DNMT1, DNMT3A, DNMT3B, MBD2, HDAC1 and MECP2. We also found MEG3 interacted with DNMT1, JAK2, STAT3, HDAC1, and TYK2, and JAK2 was bound to STAT3, STAT5 and MYC. More interestingly, JAK2 was bound to TYK2 by the bridge of MEG3. Interpretation: LncRNA MEG3 and its target miR-147 may serve as a novel therapeutic target for CML blast crisis, and chidamide might have a potential clinical application in treating CML blast crisis. Keywords: lncRNA MEG3, Chronic myeloid leukemia blast crisis, Chidamide, miR147 and epigenetic |
Databáze: | OpenAIRE |
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