Type

Journal Article

Authors

R L Stallings
A M Davidoff
A O'Meara
I M Bray
J Lynch
L Creevey
M Meehan
K Bryan
J Fay
A Tivnan
and 1 others

Subjects

Biochemistry

Topics
etoposide pharmacology mortality gene expression regulation neoplastic cisplatin mirn204 microrna human animals drug resistance neoplasm receptor trkb disease models animal kaplan meier estimate apoptosis analysis of variance membrane glycoproteins mice mice scid humans metabolism predictive value of tests protein tyrosine kinases real time polymerase chain reaction disease free survival ntrk2 protein mouse bcl2 protein mouse proto oncogene proteins reverse transcriptase polymerase chain reaction down regulation drug effects micrornas genetics drug therapy cell line tumor mice inbred strains up regulation proportional hazards models cell survival neuroblastoma antineoplastic agents

MicroRNA-204 increases sensitivity of neuroblastoma cells to cisplatin and is associated with a favourable clinical outcome. (2012)

Abstract Neuroblastoma remains a major cause of cancer-linked mortality in children. miR-204 has been used in microRNA expression signatures predictive of neuroblastoma patient survival. The aim of this study was to explore the independent association of miR-204 with survival in a neuroblastoma cohort, and to investigate the phenotypic effects mediated by miR-204 expression in neuroblastoma. Neuroblastoma cell lines were transiently transfected with miR-204 mimics and assessed for cell viability using MTS assays. Apoptosis levels in cell lines were evaluated by FACS analysis of Annexin V-/propidium iodide-stained cells transfected with miR-204 mimics and treated with chemotherapy drug or vehicle control. Potential targets of miR-204 were validated using luciferase reporter assays. miR-204 expression in primary neuroblastoma tumours was predictive of patient event-free and overall survival, independent of established known risk factors. Ectopic miR-204 expression significantly increased sensitivity to cisplatin and etoposide in vitro. miR-204 direct targeting of the 3' UTR of BCL2 and NTRK2 (TrkB) was confirmed. miR-204 is a novel predictor of outcome in neuroblastoma, functioning, at least in part, through increasing sensitivity to cisplatin by direct targeting and downregulation of anti-apoptotic BCL2. miR-204 also targets full-length NTRK2, a potent oncogene involved with chemotherapy drug resistance in neuroblastoma.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

R L Stallings, A M Davidoff, A O'Meara, I M Bray, J Lynch, L Creevey, M Meehan, K Bryan, J Fay, A Tivnan and 1 others

Experts in our system

1
Raymond L Stallings
Royal College of Surgeons in Ireland
Total Publications: 59
 
2
Isabella Bray
Royal College of Surgeons in Ireland
Total Publications: 35
 
3
Kenneth Bryan
Royal College of Surgeons in Ireland
Total Publications: 36
 
4
Joanna Fay
Royal College of Surgeons in Ireland
Total Publications: 24
 
5
Amanda Tivnan
Royal College of Surgeons in Ireland
Total Publications: 15