Targeting NAT10 Induces Apoptosis by Enhancing Endoplasmic Reticulum Stress in Acute Myeloid Leukemia Cells

Background: N-acetyltransferase 10 (NAT10) is a nucleolar protein which considered as an oncogene in many tumors and plays an important role in different cellular biological processes. However the roles of NAT10 in acute myeloid leukemia (AML) remains obscure. Methods: The expression of NAT10 in the AML patients was detected by Quantitative real-time polymerase chain reaction (q-PCR). The effect and mechanism of NAT10 on apoptosis of AML cells was evaluated by CCK-8 assay, Flow cytometry analysis and Western blot assays. Finding: It was found that NAT10 expression was significantly up-regulated in AML patients compared with health donors. NAT10 knockdown and its pharmacotherapeutic inhibitor treatment significantly increased cell cycle arrest in G1 phase, and cell proliferation arrest in AML cells. NAT10 inhibition also enhanced PERK expression, indicating that apoptosis induced by NAT10 down-regulation may caused by endoplasmic reticulum (ER) stress in the cells. Interpretation: Our results indicated NAT10 is signicantly increased in AML patients, targeting NAT10 induces cell proliferation arrest and apoptosis by enhancing ER stress in AML. Our data also reveal the oncogenic effect of NAT10 in AML and potential therapeutic effect of NAT10 inhibitor in AML. Funding Statement: This work is supported in part by The National Natural Science Foundation of China (81770172); Jiangsu Provincial Special Program of Medical Science (BE2017747); Jiangsu Province 333 project(BRA2019103); Southeast University - China Pharmaceutical University Joint Research Project(2242019K3DZ02); Milstein Medical Asian American Partnership (MMAAP) Foundation Research Project Award in Hematology (2017); Key Medical of Jiangsu Province(ZDXKB2016020). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: The study was approved by the Ethics Committee of ZhongDa Hospital of Dongnan University.