Cytoplasmic Expression of TP53INP2 Modulated by Demethylase FTO and Mutant NPM1 Promotes Autophagy in Leukemia Cells

作者全名："Huang, Junpeng; Sun, Minghui; Tao, Yonghong; Ren, Jun; Peng, Meixi; Jing, Yipei; Xiao, Qiaoling; Yang, Jing; Lin, Can; Lei, Li; Yang, Zailin; Zhang, Ling"

作者地址："[Huang, Junpeng; Sun, Minghui; Tao, Yonghong; Ren, Jun; Peng, Meixi; Jing, Yipei; Xiao, Qiaoling; Yang, Jing; Lin, Can; Lei, Li; Zhang, Ling] Chongqing Med Univ, Coll Lab Med, Key Lab Lab Med Diagnost Designated, Minist Educ, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Yang, Zailin] Chongqing Univ, Canc Hosp, Dept Hematol Oncol, Chongqing Key Lab Translat Res Canc Metastasis & I, Chongqing 400030, Peoples R China"

通信作者："Zhang, L (通讯作者)，Chongqing Med Univ, Coll Lab Med, Key Lab Lab Med Diagnost Designated, Minist Educ, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

ESI学科分类：CHEMISTRY

WOS号：WOS:000920279800001

JCR分区：Q2

影响因子：5.6

年份：2023

卷号：24

期号：2

开始页：　

结束页：　

文献类型：Article

关键词：acute myeloid leukemia; nucleophosmin 1; TP53INP2; autophagy; N-6-methyladenosine

摘要："Acute myeloid leukemia (AML) with a nucleophosmin 1 (NPM1) mutation is a unique subtype of adult leukemia. Recent studies show that NPM1-mutated AML has high autophagy activity. However, the mechanism for upholding the high autophagic level is still not fully elucidated. In this study, we first identified that tumor protein p53 inducible nuclear protein 2 (TP53INP2) was highly expressed and cytoplasmically localized in NPM1-mutated AML cells. Subsequent data showed that the expression of TP53INP2 was upregulated by fat mass and obesity-associated protein (FTO)-mediated m(6)A modification. Meanwhile, TP53INP2 was delocalized to the cytoplasm by interacting with NPM1 mutants. Functionally, cytoplasmic TP53INP2 enhanced autophagy activity by promoting the interaction of microtubule-associated protein 1 light chain 3 (LC3) - autophagy-related 7 (ATG7) and further facilitated the survival of leukemia cells. Taken together, our study indicates that TP53INP2 plays an oncogenic role in maintaining the high autophagy activity of NPM1-mutated AML and provides further insight into autophagy-targeted therapy of this leukemia subtype."

基金机构："National Natural Science Foundation of China [NSFC82072353, NSFC81873973]; Natural Science Foundation of Chongqing [cstc2021jcyj-msxmX0363]"

基金资助正文：This work was supported by National Natural Science Foundation of China (Grant No. NSFC82072353 and Grant No. NSFC81873973); Natural Science Foundation of Chongqing (Grant No: cstc2021jcyj-msxmX0363).