Comprehensive high-throughput meta-analysis of differentially expressed microRNAs in transcriptomic datasets reveals significant disruption of MAPK/JNK signal transduction pathway in Adult T-cell leukemia/lymphoma

The enriched pathways and highlighted genes in this study revealed novel disruptions in cell signaling cascades which were confirmed by real time-PCR

Shahrzad Shadabi; Nargess Delrish; Mehdi Norouzi; Maryam Ehteshami; Fariba Habibian-Sezavar; Samira Pourrezaei; Mobina Madihi; Mohammadreza Ostadali; Foruhar Akhgar; Ali Shayeghpour; Cobra Razavi Pashabayg; Sepehr Aghajanian; Sayed-Hamidreza Mozhgani; Seyed-Mohammad Jazayeri


Scholarcy highlights

  • Human T lymphotropic virus 1 is a singlestranded positive-strand RNA virus, which primarily infects CD4+ T-cells in humans
  • Further analysis revealed the first 5 of differentially expressed miRNAs were directly associated with previously identified pathways in the pathogenesis of Human T-lymphotropic virus 1
  • Network analysis demonstrated the involvement of target gene hubs in several signaling cascades, mainly in the MAPK pathway
  • After removal of redundancy, application of inclusion and exclusion criteria, and quality control using MetaQC package in R, 3 datasets namely, GSE28626, GSE31629, and GSE11577 were selected for the DEM analysis of Adult T-cell leukemia/lymphoma patients vs healthy individuals
  • The primary analysis of microarray datasets identified hsa-let-7a, hsa-let-7g, hsa-mir-181b, hsa-mir-26b, hsamir-30c, hsa-mir-186, hsa-mir-10a, hsa-mir-30b, and hsa-let-7f as DEMs in ATLL patients compared to normal individuals
  • Therapeutic targeting of JNK pathway proves to be an interesting topic for future studies. In this high throughput meta-analysis, we identified significant disruption of genes related to cell cycle, proliferation, and signal transduction in ATLL
  • Further studies are needed to identify novel and reliable biomarkers, and prognostic factors and to obtain a comprehensive mapping of deregulated biological pathways in Adult T-cell leukemia/lymphoma

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