title: Aurora-A promotes chemoresistance in hepatocelluar carcinoma by targeting NF-kappaB/microRNA-21/PTEN signaling pathway.
abstract: Hepatocellular carcinoma (HCC) is highly resistant to chemotherapy. Previously, we have shown that Aurora-A mRNA is upregulated in HCC cells or tissues and silencing of Aurora-A using small interfering RNA (siRNA) decreases growth and enhances apoptosis in HCC cells. However, the clinical significance of Aurora-A protein expression in HCC and association between Aurora-A expression and HCC chemoresistance is unclear. Here, we showed that Aurora-A protein is upregulated in HCC tissues and significantly correlated with recurrence-free and overall survival of patients and multivariate analysis indicated that immunostaining of Aurora-A will be an independent prognostic factor for patients. Silencing of Aurora-A significantly increased the chemosensitivity of HCC cells both in vitro and in vivo, while overexpression of Aurora-A induced the opposite effects. Furthermore, overexpression of Aurora-A reduces chemotherapy-induced apoptosis by promoting microRNA-21 expression, which negatively regulates PTEN and then inhibits caspase-3-mediated apoptosis induction. Mechanically, we demonstrated that Aurora-A promotes expression of nuclear Ikappaβ-alpha (Iκβα) protein and enhances NF-kappa B (NF-κB) activity, thus promotes the transcription of miR-21. This study first reported the involvement of Aurora-A/NF-κB/miR-21/PTEN/Akt signaling axis in chemoresistance of HCC cells, suggesting that targeting this signaling pathway would be helpful as a therapeutic strategy for the reversal of chemoresistance in HCC.
authors.affiliation: Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Dongqin
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Jiayuan
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Feng
authors.affiliation: Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Siqi
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Yitian
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Haizhu
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Wei
authors.initials: W
authors.lastname: De
authors.affiliation: Department of Hepatobiliary Surgery, First Hospital Affiliated to the Chinese PLA General Hospital, Fucheng, Haidian District, Beijing, China.
authors.forename: Ziman
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Longbang
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D064096:Aurora Kinase A / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D056945:Hep G2 Cells; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; C576917:AURKA protein, human; D064096:Aurora Kinase A; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human