title: Depletion of Aurora A leads to upregulation of FoxO1 to induce cell cycle arrest in hepatocellular carcinoma cells.
abstract: Aurora A kinase has drawn considerable attention as a therapeutic target for cancer therapy. However, the underlying molecular and cellular mechanisms of the anticancer effects of Aurora A kinase inhibition are still not fully understood. Herein, we show that depletion of Aurora A kinase by RNA interference (RNAi) in hepatocellular carcinoma (HCC) cells upregulated FoxO1 in a p53-dependent manner, which induces cell cycle arrest. Introduction of an RNAi-resistant Aurora A kinase into Aurora A-knockdown cells resulted in downregulation of FoxO1 expression and rescued proliferation. In addition, silencing of FoxO1 in Aurora A-knockdown cells allowed the cells to exit cytostatic arrest, which, in turn, led to massive cell death. Our results suggest that FoxO1 is responsible for growth arrest at the G2/M phase that is induced by Aurora A kinase inhibition.
authors.affiliation: Biomedical Research Center Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea. symoonlee@pusan.ac.kr
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Gong Rak
authors.initials: GR
authors.lastname: Lee
authors.forename: Dong-Hyuk
authors.initials: DH
authors.lastname: Woo
authors.forename: Neung Hwa
authors.initials: NH
authors.lastname: Park
authors.forename: Hee Jeong
authors.initials: HJ
authors.lastname: Cha
authors.forename: Yong-Hwan
authors.initials: YH
authors.lastname: Moon
authors.forename: In-Seob
authors.initials: IS
authors.lastname: Han
mesh_terms: D017209:Apoptosis; D064127:Aurora Kinases; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D059565:G2 Phase Cell Cycle Checkpoints; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D059566:M Phase Cell Cycle Checkpoints; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases