Network analysis of microRNAs, genes and their regulation in diffuse and follicular B-cell lymphomas
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Oshrat Hershkovitz-Rokah1,2,3,*, Polina Geva1,*, Mali Salmon-Divon1, Ofer Shpilberg2,3,4 and Stella Liberman-Aronov1
1Department of Molecular Biology, Faculty of Natural Sciences, Ariel University, Ariel, Israel
2Translational Research Laboratory, Assuta Medical Centers, Tel Aviv, Israel
3Institude of Hematology, Assuta Medical Centers, Tel Aviv, Israel
4Pre-Medicine Department, School of Health Sciences, Ariel University, Ariel, Israel
*These authors have contributed equally to this work
Stella Liberman-Aronov, email: [email protected]
Keywords: miRNA signature; DLBCL; FL; miRNA-mRNA pairing; B cell lymphoma
Received: June 14, 2017 Accepted: December 21, 2017 Published: January 05, 2018
MicroRNAs (miRs) are short non-coding regulatory RNAs that control gene expression at the post-transcriptional level and play an important role in cancer development and progression, acting either as oncogenes or as tumor suppressors. Identification of aberrantly expressed miRs in patients with hematological malignancies as compared to healthy individuals has suggested that these molecules may serve as novel clinical diagnostic and prognostic biomarkers.
We conducted a systematic literature review of articles published between 2007 and 2017 and re-analyzed experimentally-validated human miR expression signatures in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) from various biological sources (tumor tissue, peripheral blood, bone marrow and cell lines). A unique miR expression pattern was observed for each disease. Compared to healthy individuals, 61 miRs were aberrantly expressed in DLBCL and 85 in FL; 20-30% of aberrantly expressed miRs overlapped between the two lymphoma subtypes.
Analysis of integrative positive and negative miRNA-mRNA relationships using the Ingenuity Pathway Analysis (IPA) system revealed 970 miR-mRNA pairs for DLBCL and 90 for FL. Through gene ontology analysis, we found potential regulatory pathways that are deregulated in DLBCL and FL due to improper expression of miR target genes. By comparing the expression level of the aberrantly expressed miRs in DLBCL to their expression levels in other malignancies, we identified seven miRs that are aberrantly expressed in DLBCL tumor tissues (miR-15a, miR-16, miR-17, miR-106, miR-21, miR-155 and miR-34a-5p). This specific expression pattern may be a potential diagnostic tool for DLBCL.
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