Serum-circulating miRNAs predict neuroblastoma progression in mouse model of high-risk metastatic disease
| Autor: | Satish Kumar Ramraj, Sheeja Aravindan, Terence S. Herman, Mohan Natarajan, Dinesh Babu Somasundaram, Natarajan Aravindan |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Oncology Circulating mirnas medicine.medical_specialty Disease Bioinformatics Mice Neuroblastoma 03 medical and health sciences Risk Factors Internal medicine microRNA Animals Humans Medicine Gene silencing Clinical significance Neoplasm Metastasis serum-circulating miRNA prognostic biomarker high-risk metastatic neuroblastoma business.industry medicine.disease 3. Good health Disease Models Animal MicroRNAs 030104 developmental biology Tumor progression miRnome profiling Disease Progression Heterografts business Research Paper Biomedical sciences |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.7615 |
| Popis: | // Satish Kumar Ramraj 1 , Sheeja Aravindan 2 , Dinesh Babu Somasundaram 1 , Terence S. Herman 1, 2 , Mohan Natarajan 3 , Natarajan Aravindan 1 1 Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA 2 Stephenson Cancer Center, Oklahoma City, OK, USA 3 Department of Pathology, University of Texas Health Sciences Center at San Antonio, San Antonio, TX, USA Correspondence to: Natarajan Aravindan, e-mail: naravind@ouhsc.edu Keywords: serum-circulating miRNA, high-risk metastatic neuroblastoma, miRnome profiling, prognostic biomarker Received: August 30, 2015 Accepted: January 19, 2016 Published: February 23, 2016 ABSTRACT Background : Circulating miRNAs have momentous clinical relevance as prognostic biomarkers and in the progression of solid tumors. Recognizing novel candidates of neuroblastoma-specific circulating miRNAs would allow us to identify potential prognostic biomarkers that could predict the switch from favorable to high-risk metastatic neuroblastoma (HR-NB). Results : Utilizing mouse models of favorable and HR-NB and whole miRnome profiling, we identified high serum levels of 34 and low levels of 46 miRNAs in animals with HR-NB. Preferential sequence homology exclusion of mouse miRNAs identified 25 (11 increased; 14 decreased) human-specific prognostic marker candidates, of which, 21 were unique to HR-NB. miRNA QPCR validated miRnome profile. Target analysis defined the candidate miRNAs’ signal transduction flow-through and demonstrated their converged roles in tumor progression. miRNA silencing studies verified the function of select miRNAs on the translation of at least 14 target proteins. Expressions of critical targets that correlate tumor progression in tissue of multifarious organs identify the orchestration of HR-NB. Significant (>10 fold) increase in serum levels of miR-381, miR-548h, and miR-580 identify them as potential prognostic markers for neuroblastoma progression. Conclusion : For the first time, we identified serum-circulating miRNAs that predict the switch from favorable to HR-NB and, further imply that these miRNAs could play a functional role in tumor progression. |
| Databáze: | OpenAIRE |
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