Ikke-kodende RNA og cytostatikaresistens ved neuroblastom
MicroRNAs and Drug Resistance in Neuroblastoma
Neuroblastoma is the most common diagnosed tumor in infants and the second most common extracranial tumor of childhood. Despite continued improvements in cancer treatment, the survival rate of patients with high-risk neuroblastoma is still very low..
esistance to antitumor agents is a major cause of treatment failure in patients with high-risk neuroblastoma. Advances in the understanding of how neuroblastoma cells become drug resistant during the course of therapy are needed to develop new anticancer drugs that improve survival of high-risk patients MicroRNAs, small RNA molecules found in all tissues, are involved in virtually all cellular processes including carcinogenesis, tumor progression and cancer drug resistance. In recent years, increasing attention has been given to the potential of microRNA-based therapy for the treatment of human cancers. MicroRNAs play a vital role in the initiation and progression of neuroblastoma. The role of microRNAs in neuroblastoma cell resistance to chemotherapeutic agents is poorly understood. However, the understanding of biological and molecular aspects of microRNA-mediated drug resistance in neuroblastoma may provide exciting opportunities for therapy of aggressive neuroblastoma. The aim of this study is to identify microRNAs that may contribute to multidrug resistance in neuroblastoma. Furthermore, it focuses on the value of microRNAs as a therapeutic option for neuroblastoma. We demonstrated that the expression level of the microRNA miR-193b increases during the course of anticancer therapy in neuroblastoma. Functional studies validated that elevated levels of miR-193b increase resistance of neuroblastoma cells to diverse anticancer drugs. A somewhat unexpected result was the finding that miR-193b effectively suppressed neuroblastoma cell growth. This effect wasobserved in all neuroblastoma cell lines tested, and independent of risk factors. Importantly, our data suggest that miR-193b as a monotherapy or in combination with BH3 mimetics may be a promising strategy to treat high-risk neuroblastoma resistant to conventional anticancer agents Sarah Andrea Roth disputerer for ph.d.-graden i helsevitenskap og vil offentlig forsvare avhandlingen: MicroRNAs and Drug Resistance in Neuroblastoma i februar 2017. The other PhD-students will work on this project the next years.
Next generation sequencing of microRNAs from isogenic neuroblastoma cell lines isolated before and after treatment.
Cancer Lett 2016 Mar 01;372(1):128-36. Epub 2015 des 17