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The Potential Contribution of Micrornas in Anti-Cancer Effects of Aurora Kinase Inhibitor (Azd1152-Hqpa) Publisher Pubmed



Zekri A1, 2 ; Mesbahi Y3, 4 ; Boustanipour E5 ; Sadr Z5 ; Ghaffari SH3, 6
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Authors Affiliations
  1. 1. Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran
  3. 3. Hematologic Malignancies Research Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
  5. 5. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran, Iran
  7. 7. Tehran University of Medical Sciences, Tehran, Iran

Source: Journal of Molecular Neuroscience Published:2018


Abstract

Neuroblastoma (NB) remains the critical challenge in pediatric oncology. It has the highest rate of spontaneous regression among all human cancers. Aurora kinase B (AURKB), a crucial regulator of malignant mitosis, is involved in chromosome segregation and cytokinesis. AZD1152-HQPA (Barasertib) is a small selective inhibitor of AURKB activity and currently bears clinical assessment for several malignancies. Studies suggested that microRNAs are involved in the pathobiology and chemoresistance of neuroblastoma. In the present study, we first investigated the restrictive potentials of AZD1152-HQPA on cell viability, colony formation, nucleus morphology, polyploidy, and cell-cycle distribution. We then studied the expressions level of 88 cancer-related miRNAs in untreated and AZD1152-HQPA-treated NB cell line (SK-N-MC) by real-time PCR using miRNA cancer-array system. After normalizing, the fold change of miRNAs was calculated in the AZD1152-HQPA-treated cell as compared to untreated. Our results demonstrate that the inhibition of AURKB by AZD1152-HQPA induced potent antitumor activity, suppressed cell survival, and triggered apoptosis and polyploidy in NB cells. AZD1152-HQPA, at a relevant concentration, modulated a substantial number of cancer-related miRNAs in NB cell. Interestingly, by screening the literature, among the 7 top AZD1152-HQPA-induced upregulated miRNAs (> 3-fold change; P < 0.01), all were potential tumor suppressors associated with cell apoptosis and cycle arrest, as well as inhibition of angiogenesis, invasion, and metastasis, while two downregulated miRNAs were known to have oncogenic function. Taken together, our study showed for the first time the potential contribution of miRNAs in the anti-cancer effects of AZD1152-HQPA. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.
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