Neuroblastoma (NB) is an enigmatic and deadliest pediatric cancer to treat. The major obstacles to the effective immunotherapy treatments in NB are defective immune cells and the immune evasion tactics deployed by the tumor cells and the stromal microenvironment. Nervous system development during embryonic and pediatric stages is critically mediated by non-coding RNAs such as micro RNAs (miR). Hence, we explored the role of miRs in anti-tumor immune response via a range of data-driven workflows andin vitro&in vivoexperiments. Using the TARGET, NB patient dataset (n=249), we applied the robust bioinformatic workflows incorporating differential expression, co-expression, survival, heatmaps, and box plots. We initially demonstrated the role of miR-15a-5p (miR-15a) and miR-15b-5p (miR-15b) as tumor suppressors, followed by their negative association with stromal cell percentages and a statistically significant negative regulation of T and natural killer (NK) cell signature genes, especially CD274 (PD-L1) in stromal-low patient subsets. The NB phase-specific expression of the miR-15a/miR-15b-PD-L1 axis was further corroborated using the PDX (n=24) dataset. We demonstrated miR-15a/miR-15b mediated degradation of PD-L1 mRNA through its interaction with the 3'-untranslated region and the RNA-induced silencing complex using sequence-specific luciferase activity and Ago2 RNA immunoprecipitation assays. In addition, we established miR-15a/miR-15b induced CD8+T and NK cell activation and cytotoxicity against NBin vitro. Moreover,injecti...
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Round-ups are the summaries of handpicked papers around trending topics published every week. These would enable you to scan through a collection of papers and decide if the paper is relevant to you before actually investing time into reading it.
Climate change Research Articles published between Jun 20, 2022 to Jun 26, 2022
Jun 27, 2022
Articles Included: 2
One eighth of the bird species in the world is considered globally threatened; the avifauna of Iraq comprises 409 species and is considered as the maj...Read More