Abstract 25P
Background
Triggering and overactivation of extracellular signal-regulated kinases/mitogen-activated protein kinase(MAPK) and phosphatidylinositol 3-kinase/protein kinase B(AKT) signaling pathways are one of the most important factors in the formation of many types of cancer, including neuroblastoma, by reducing the effectiveness of treatment and contributing to development of resistance to chemotherapy during the treatment process. There is evidence reinforcing the possibility that these two signaling pathways are communicating and interacting with each other in carcinogenic process. Yet it is unknown what is there at the heart of this interaction. There are studies giving insights about certain cell cycle regulators such as Speedy/RINGO which may be involved in the intersection of these signaling pathways. In these studies, connection of Speedy/RINGO with AKT and MAPK pathways is studied partially and also these studies are performed with cell and tissue types other than neuroblastoma. Thus, to date there is not any data available showing the connective role of Speedy/RINGO in between AKT and MAPK pathways and the aim of this study is to show the connective role of Speedy/RINGO between AKT and MAPK pathways in neuroblastoma cells.
Methods
In this study, MAPK pathway was firstly inhibited with U0126 chemical and expression of Speedy/RINGO was analyzed. A corresponding decrease in the expression of Speedy/RINGO and phosphorylation of AKT were shown. This data was confirmed with siRNA silencing of Speedy/RINGO.
Results
Showed that Speedy/RINGO inhibition caused a significant decrease in CyclinA and CDK2 expression levels and AKT phosphorylation amounts. It has also shown that these inhibition treatments significantly reduce the viability of cancer cells.
Conclusions
All data obtained from this study provide crucial information for the first time about the connecting and overactivating function of Speedy/RINGO in between AKT and MAPK pathways, thereby giving insights to choose appropriate molecular targets for diagnosis and treatment of many cancer types.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
This work was supported by the Scientific Research Project Office of Mugla Sitki Kocman University (Project Numbers 17/251 and 17/023).
Disclosure
All authors have declared no conflicts of interest.