c-Myc suppresses miR-451⊣YWTAZ/AKT axis via recruiting HDAC3 in acute myeloid leukemia

摘要: // Rui Su 1 , Jia-Nan Gong Ming-Tai Chen Li Song Chao Shen Xin-Hua Zhang 2 Xiao-Lin Yin Hong-Mei Ning 3 Bing Liu 4 Fang Wang Yan-Ni Ma Hua-Lu Zhao Jia Yu Jun-Wu The State Key Laboratory of Medical Molecular Biology, Department Biochemistry and Institute Basic Sciences, Chinese Academy Sciences Peking Union College, Beijing, China Hematology, 303 Hospital, Nanning, Guangxi, Hematopoietic Stem Cell Transplantation, Affiliated Hospital to Military 307 Proteomics, Translational Medicine Center Cells, 307-lvy Center, Oncology, Correspondence to: Zhang, email: junwu_zhang@pumc.edu.cn Keywords: acute myeloid leukemia, microRNA-451, c-Myc, HDAC3, YWHAZ Received: February 20, 2016      Accepted: September Published: October 15, 2016 ABSTRACT Aberrant activation c-Myc plays an important oncogenic role via regulating a series coding non-coding genes in leukemia (AML). Histone deacetylases (HDACs) can remove acetyl group from histone regulate gene expression changing chromatin structure. Here, we found miR-451 is abnormally down-regulated AML patient samples; recruits HDAC3 form transcriptional suppressor complex, co-localizes on the promoter, epigenetically inhibits its transcription finally induces downregulation AML. Furthermore, our in vitro vivo results suggest that functions as tumor promoting apoptosis suppressing malignant cell proliferation. mechanistic study demonstrated directly targets mRNA suppresses YWHAZ/AKT signaling Knockdown restoration inhibition signaling. In patients, low level negatively correlated with high levels YWHAZ, while positively related expression. These suggested c-Myc⊣miR-451⊣YWHAZ/AKT cascade might play crucial during leukemogenesis, reintroduction could be potential strategy for therapy.