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. 2021 Jan;147(1):33-47.
doi: 10.1007/s00432-020-03373-w. Epub 2020 Sep 3.

High Wilms' tumor 1 associating protein expression predicts poor prognosis in acute myeloid leukemia and regulates m6A methylation of MYC mRNA

Duolan Naren #  1 , Tianyou Yan #  1 , Yuping Gong  2 , Jingcao Huang  1 , Dan Zhang  1 , Lina Sang  1 , Xue Zheng  1 , Yarong Li  1
Affiliations

High Wilms' tumor 1 associating protein expression predicts poor prognosis in acute myeloid leukemia and regulates m6A methylation of MYC mRNA

Duolan Naren et al. J Cancer Res Clin Oncol. 2021 Jan.

Abstract

Purpose: Acute myeloid leukemia (AML) is a heterogenous disease and the survival of AML patients is largely attributed to the improvement of supportive treatment. Wilms' tumor 1-associated protein (WTAP) is a nuclear protein functions in many physiological and pathological processes. Although its expression and function in many malignant diseases have been reported, its prognostic and epigenetic roles in AML are largely unknown.

Methods: Peripheral blood or bone marrow samples were collected from AML patients. The WTAP expression was detected by western blot. WTAP expression level and patients clinical features were analyzed using statistical methods. WTAP knockdown AML cells were constructed. The experiments on proliferation, tumorigenic ability, cell cycle, and apoptosis were performed. Transcriptome sequencing was performed and analyzed. M6A methylation level was measured and m6A-RIP was performed to quantify m6A methylation level of MYC mRNA. RNA stability assay was performed to measure the half-life of mRNA.

Results: WTAP was overexpressed in AML patients and was an independent poor-risk factor in AML (p = 0.0140). Moreover, we found that WTAP regulated proliferation, tumorigenesis, cell cycle, and differentiation of AML cells. Furthermore, WTAP made AML cells resistant to daunorubicin. In further investigations, m6A methylation level was downregulated when knocking down WTAP, and c-Myc was upregulated due to the decreased m6A methylation of MYC mRNA.

Conclusion: High WTAP expression predicts poor prognosis in AML and WTAP plays an epigenetic role in AML.

Keywords: Acute myeloid leukemia; Epigenetics; Wilms’ tumor 1-associated protein; m6A methylation.

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