Overexpression of Exportin-5 Overrides the Inhibitory Effect of miRNAs Regulation Control and Stabilize Proteins via Posttranslation Modifications in Prostate Cancer
| Autor: | David J. Clark, Paul Aiyetan, Naseruddin Höti, Ronald Rodriguez, Tamara Jane Johnson, Hui Zhang, Binod Kumar, Punit Shah, Shuang Yang, Wasim H. Chowdery, Arife Unal Eroglu, Yingwei Hu |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Biology lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Bioinformatics medicine.disease lcsh:RC254-282 XPO5 3. Good health Cellular protein 03 medical and health sciences Prostate cancer 030104 developmental biology medicine.anatomical_structure microRNA Cancer research medicine Posttranslational modification MiRNA biogenesis Fibroblast Inhibitory effect |
| Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 19, Iss 10, Pp 817-829 (2017) |
| ISSN: | 1476-5586 |
| DOI: | 10.1016/j.neo.2017.07.008 |
| Popis: | Although XPO5 has been characterized to have tumor-suppressor features in the miRNA biogenesis pathway, the impact of altered expression of XPO5 in cancers is unexplored. Here we report a novel "oncogenic" role of XPO5 in advanced prostate cancer. Using prostate cancer models, we found that excess levels of XPO5 override the inhibitory effect of the canoncial miRNA-mRNA regulation, resulting in a global increase in proteins expression. Importantly, we found that decreased expression of XPO5 could promote an increase in proteasome degradation, whereas overexpression of XPO5 leads to altered protein posttranslational modification via hyperglycosylation, resulting in cellular protein stability. We evaluated the therapeutic advantage of targeting XPO5 in prostate cancer and found that knocking down XPO5 in prostate cancer cells suppressed cellular proliferation and tumor development without significantly impacting normal fibroblast cells survival. To our knowledge, this is the first report describing the oncogenic role of XPO5 in overriding the miRNAs regulation control. Furthermore, we believe that these findings will provide an explanation as to why, in some cancers that express higher abundance of mature miRNAs, fail to suppress their potential protein targets. |
| Databáze: | OpenAIRE |
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