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

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. MA methylation level was measured and mA-RIP was performed to quantify mA 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, mA methylation level was downregulated when knocking down WTAP, and c-Myc was upregulated due to the decreased mA methylation of MYC mRNA.

CONCLUSION

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