title: Aurora-B and HDAC synergistically regulate survival and proliferation of lymphoma cell via AKT, mTOR and Notch pathways.
abstract: Aurora-B is a protein kinase that functions mainly in the attachment of the mitotic spindle to the centromere. Overexpression of Aurora-B causes unequal distribution of genetic information, creating aneuploidy cells, a hallmark of cancer. Histone deacetylases (HDACs) are a class of enzymes that remove acetyl groups from a ε-N-acetyl lysine amino acid on a histone, allowing the histones to wrap the DNA more tightly, thus globally regulating gene transcription. Additionally, these HDACs can also modify non-histone proteins. Inhibition of HDACs is a potent strategy for cancer treatment. Here, we report that inhibition of Aurora-B and HDAC exerts similar tumor suppressive effects in cells. Knockdown of Aurora-B or inhibition of HDAC achieved the same effect on repression of cell proliferation. Furthermore, we found that the tumor suppressive effect of Aurora-B and HDAC inhibition is due to the induction of cell cycle arrest and/or apoptosis. Mechanistically, we demonstrated that Aurora-B and HDAC can cooperatively regulate AKT, mTOR and Notch pathways.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou Jianshe East Road, Zhengzhou 450052, Henan Province, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou Jianshe East Road, Zhengzhou 450052, Henan Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou Jianshe East Road, Zhengzhou 450052, Henan Province, China.
authors.forename: Weijie
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou Jianshe East Road, Zhengzhou 450052, Henan Province, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou Jianshe East Road, Zhengzhou 450052, Henan Province, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou Jianshe East Road, Zhengzhou 450052, Henan Province, China. Electronic address: liuyanfang018@163.com.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D064107:Aurora Kinase B / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D055785:Gene Knockdown Techniques; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D008223:Lymphoma / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D056572:Histone Deacetylase Inhibitors; D034741:RNA, Small Interfering; D051880:Receptors, Notch; C576921:AURKB protein, human; D064107:Aurora Kinase B; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D006655:Histone Deacetylases
keywords: Apoptosis; Aurora-B; Cell cycle; Histone deacetylase; lymphoma