University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

Program in Bioinformatics and Integrative Biology; Program in Molecular Medicine; Division of Transfusion Medicine, Department of Medicine

Publication Date

3-28-2017

Document Type

Article

Disciplines

Bioinformatics | Cancer Biology | Computational Biology | Hemic and Lymphatic Diseases | Microbiology | Virus Diseases

Abstract

Endemic Burkitt lymphoma (eBL) is an aggressive B cell lymphoma and is associated with Epstein-Barr virus (EBV) and Plasmodium falciparum malaria co-infections. Central to BL oncogenesis is the over-expression of the MYC proto-oncogene which is caused by a translocation of an Ig enhancer in approximation to the myc gene. While whole genome/transcriptome sequencing methods have been used to define driver mutations and transcriptional dysregulation, microRNA (miRNA) dysregulation and differential expression has yet to be fully characterized. We hypothesized that both human and EBV miRNAs contribute to eBL clinical presentation, disease progression, and poor outcomes. Using sensitive and precise deep sequencing, we identified miRNAs from 17 Kenyan eBL patient tumor samples and delineated the complement of both host and EBV miRNAs. One human miRNA, hsa-miR-10a-5p was found to be differentially expressed (DE), being down-regulated in jaw tumors relative to abdominal and in non-survivors compared to survivors. We also examined EBV miRNAs, which made up 2.7% of the miRNA composition in the eBL samples. However, we did not find any significant associations regarding initial patient outcome or anatomical presentation. Gene ontology analysis and pathway enrichment of previously validated targets of miR-10a-5p suggest that it can promote tumor cell survival as well as aid in evasion of apoptosis. To examine miR-10a-5p regulatory effect on gene expression in eBL, we performed a pairwise correlation coefficient analysis on the expression levels of all its validated targets. We found a significant enrichment of correlated target genes consistent with miR-10a-5p impacting expression. The functions of genes and their correlation fit with multiple target genes impacting tumor resilience. The observed downregulation of miR-10a and associated genes suggests a role for miRNA in eBL patient outcomes and has potential as a predictive biomarker that warrants further investigation.

Keywords

EBV, RNAseq, endemic Burkitt lymphoma, miR-10a-5p, microRNA expression

Rights and Permissions

Copyright © 2017 Oduor, Movassagh, Kaymaz, Chelimo, Otieno, Ong'echa, Moormann and Bailey. Citation: Front Microbiol. 2017 Mar 28;8:501. doi: 10.3389/fmicb.2017.00501. eCollection 2017. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Frontiers in microbiology

PubMed ID

28400759

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

 
 

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