1. Academic Validation
  2. The Long Noncoding RNA MEG3 and its Target miR-147 Regulate JAK/STAT Pathway in Advanced Chronic Myeloid Leukemia

The Long Noncoding RNA MEG3 and its Target miR-147 Regulate JAK/STAT Pathway in Advanced Chronic Myeloid Leukemia

  • EBioMedicine. 2018 Aug;34:61-75. doi: 10.1016/j.ebiom.2018.07.013.
Zi-Ye Li 1 Lin Yang 1 Xiao-Jun Liu 1 Xing-Zhe Wang 1 Yu-Xia Pan 1 Jian-Min Luo 2
Affiliations

Affiliations

  • 1 Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China.
  • 2 Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China. Electronic address: zymhbsjz@163.com.
Abstract

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

Chidamide; Chronic myeloid leukemia blast crisis; lncRNA MEG3; miR147 and epigenetic.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-109015
    98.70%, HDAC Inhibitor