ELK1-Induced upregulation of long non-coding TNK2-AS1 promotes the progression of acute myeloid leukemia by EZH2-mediated epigenetic silencing of CELF2

被引:4
作者
Guo, Dongfang [1 ]
Zhang, Airong [1 ]
Suo, Meifang [1 ]
Wang, Ping [2 ]
Liang, Yile [3 ]
机构
[1] Zhumadian Cent Hosp, Dept Clin Lab, Zhumadian, Peoples R China
[2] Zhumadian Cent Hosp, Dept Hematopathol, Zhumadian, Peoples R China
[3] Henan Univ Sci & Technol, Dept Infect Dis, Affiliated Hosp 1, Luoyang, Peoples R China
关键词
LncRNA TNK2-AS1; ELK1; EZH2; CELF2; acute myeloid leukemia; BINDING PROTEIN CELF2; RNA;
D O I
10.1080/15384101.2022.2109898
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Acute myeloid leukemia (AML) is the second most common hematological malignancy after lymphoma in the world. Long non-coding RNAs (LncRNAs) have been suggested as key regulators of cancer development and progression in AML. As a member of lncRNA family, the biological role and mechanisms of tyrosine kinase non receptor 2 antisense RNA 1 (TNK2-AS1) in AML is still unclear. The expression of TNK2-AS1 was measured with RT-qPCR in AML cell lines. The changes of the proliferation, apoptosis, and differentiation in TNK2-AS1 shRNA-transfected HL-60 and THP-1 cells were detected with CCK-8, EdU, flow cytometry, Western blot, and NBT assays. Molecular control of TNK2-AS1 on CUGBP Elav-like family member 2 (CELF2) and ETS domain-containing protein-1 (ELK1) on TNK2-AS1 was assessed by chromatin immunoprecipitation (ChIP), RT-qPCR, Western blot, and RNA immunoprecipitation (RIP) assays. TNK2-AS1 expression was upregulated in AML cell lines and negatively correlated with survival patients. Knockdown of TNK2-AS1 markedly reduced AML cell proliferation and promoted apoptosis and differentiation. Likewise, TNK2-AS1 knockdown significantly suppressed tumor growth in vivo. Mechanistically, the upregulation of TNK2-AS1 was activated by transcription factor ELK1. We also uncovered that TNK2-AS1 exerted tumor-promoting effect through silencing CELF2 via binding with EZH2, thus activating PI3K/Akt pathway in AML cells. Elevated expression of TNK2-AS1 was induced by ELK1 and facilitated AML progression by suppressing CELF2 expression via EZH2-mediated epigenetic silencing, suggesting TNK2-AS1 may be a promising therapeutic target and prognostic marker for AML patients.
引用
收藏
页码:117 / 130
页数:14
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