Speedy/RINGO protein interacts with ERK/MAPK and PI3K/AKT pathways in SH-SY5Y neuroblastoma cells
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Speedy/RINGO protein interacts with ERK/MAPK and PI3K/AKT pathways in SH‑SY5Y neuroblastoma cells Yesim Kaya1 · Seren Kucukvardar1,2 · Aysegul Yildiz1 Received: 3 May 2020 / Accepted: 19 June 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Abnormal activity of ERK/MAPK and PI3K/AKT pathways is one of the most important factors for the development of many cancer types including neuroblastoma cancer. Apart from these two pathways, some cell cycle regulators such as Speedy/RINGO also contribute to neuroblastoma development. There is data reinforcing the possible communication of the components of ERK/MAPK and PI3K/AKT pathways in carcinogenic process. In addition to this, there are studies about the direct/indirect interaction of Speedy/RINGO with these pathways in different cell types other than neuroblastoma. However, there is not any study available showing the interaction of Speedy/RINGO with both pathways in neuroblastoma cells. Therefore, the aim of this study is to determine the possible effect of Speedy/RINGO on PI3K/AKT and ERK/MAPK pathways in SH-SY5Y neuroblastoma cells. For this aim, Speedy/RINGO was silenced by siRNA technique to analyze the effects of direct inhibition of Speedy/RINGO on these pathways. Results showed that Speedy/RINGO silencing caused a significant decrease in MEK1/2 expression and AKT phosphorylation. Afterward, MEK1/2 was inhibited using a specific inhibitor U0126. Data reveal a corresponding decrease in the Speedy/RINGO expression and AKT phosphorylation indicating a reciprocal interaction between ERK/MAPK and Speedy/RINGO. In addition, MTS analysis showed that both ERK/ MAPK inhibition and Speedy/RINGO silencing significantly reduced the viability of SH-SY5Y cells. This study provides information about a possible interaction of Speedy/RINGO with PI3K/AKT and ERK/MAPK pathways in SH-SY5Y cells for the first time. It will not only help to better understand the cancer-prone interactions of these pathways but also enable us to identify the appropriate molecular targets for developing efficient treatment strategies. Keywords Neuroblastoma · SH-SY5Y · PI3K/AKT · ERK/MAPK · Speedy/RINGO
Introduction Neuroblastoma is the most common extracranial solid tumor among newborns and children [1]. One of the most important factors of the disease is the dysregulation of extracellular signal-regulated kinases/mitogen-activated protein kinase (ERK/MAPK) and phosphatidylinositol 3-kinase/ protein kinase B (PI3K/AKT) signaling pathways [2, 3]. A recent study showed that ERK/MAPK signaling pathway is highly activated in neuroblastoma primary tumor cells [4], * Aysegul Yildiz [email protected] 1
Department of Molecular Biology and Genetics, Faculty of Science, Mugla Sitki Kocman University, Mugla, Turkey
Department of Molecular Biology‑Genetics and Biotechnology, Faculty of Science and Letters, Istanbul Technical University, Istanbul, Turkey
2
while another study indicated that the PI3K/AKT signaling pathway was significantly activated in neuroblastoma
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