Global gene expression changes caused by vtRNA2-1/nc886 in Prostate Cancer

Non-coding RNA 886 has emerged as a pivotal regulatory RNA with distinct functions across various tissues. While it is well recognized as a tumor suppressor in prostate cancer, the underlying molecular mechanisms remain elusive. This study used a multi-omics approach to delineate the principal pathways influenced by nc886 in prostate cancer. We conducted transcriptomic and proteomic analyses on malignant DU145, LNCaP, PC3, and benign RWPE-1 prostate cell lines transiently transfected with either in vitro transcribed nc886 or corresponding antisense oligonucleotides. A significant enrichment in immune system related pathways , particularly interferon signaling, was observed across the cell lines. Furthermore, proteomics identified new pathways that nc886 might regulate. Validation through luciferase reporter gene assays on IFN-B promoter and Interferon-Stimulated Response Elements confirmed the upregulation of the interferon response. Intriguingly, the phosphorylation state of PKR and NFkappaB-responsive promoter activity did not vary during these experiments, suggesting that nc886 is acting in a PKR-independent manner; this is consistent with activation, rather than inhibition of interferon response expected from the nc886-mediated PKR inhibition previously described. To assess the clinical significance of these findings, we performed a Gene Set Enrichment Analysis on the PRAD-TCGA dataset using RNA-seq and DNA methylation data. A positive correlation between the inferred nc886 expression and the activation of immune-related pathways in the tissue samples was found, suggesting that nc886 enhances immunity also in the clinical setting. Overall, our study supports the tumor suppressive function of nc886, where its downregulation in the tumor may lead to a blunted immune response.