title: Aurora kinase A mediates c-Myc's oncogenic effects in hepatocellular carcinoma.
abstract: Dysregulation of c-Myc (Myc) has been shown to contribute to progression of hepatocellular carcinoma, however, the detailed molecular mechanism remains poorly understood. Here, we report that Myc binds to the Aurora kinase A (Aurka) promoter and induces expression of Aurka in HCC cells. Increased expression of Aurka correlates with that of Myc in HCC. Nuclear accumulation of Aurka was confirmed by subcellular protein fractionation and immunoblot experiments in HCC cells. Myc inhibition decreases the nuclear accumulation of Aurka in HCC cells. Also Aurka accumulating in the nucleus up-regulates Myc transcription by binding the Myc promoter containing the highly conserved CCCTCCCCA in the NHE region of the CpG islands. Inhibition of Myc or Aurka diminishes the malignant phenotypes of HCC cells by down-regulating some common target genes. Also Aurka and Myc mediates the effects of each other, at least partially, on proliferation, anchorage-independent soft agar growth, and ATP production. Blocking Aurka in an orthotopic model significantly impairs tumor growth in mice. These results identify a Myc-Aurka feedback loop in which Myc and Aurka regulate expression of each other at the transcriptional level and both play an important role in hepatocarcinogenesis.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Longfeng
authors.initials: L
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Han
authors.initials: H
authors.lastname: Han
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Surgery, Wuhan Union Hospital, Wuhan, China.
authors.forename: Jinxiang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Zhongnan Hospital, Wuhan University, Wuhan, China.
authors.forename: Maohui
authors.initials: M
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Youjun
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D064096:Aurora Kinase A / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011401:Promoter Regions, Genetic / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; C576917:AURKA protein, human; D064096:Aurora Kinase A
keywords: aurora kinase A; autophagy; c-Myc; hepatocellular carcinoma; malignant phenotypes