Multi-Omics Study Reveals Nc886/vtRNA2-1 as a Positive Regulator of Prostate Cancer Cell Immunity

Noncoding RNA 886 has emerged as a pivotal regulatory RNA with distinct functions across tissues, acting as a regulator of protein activity by directly binding to protein partners. While it is well recognized as a tumor suppressor in prostate cancer, the underlying molecular mechanisms remain elusive. To discover the principal pathways regulated by nc886 in prostate cancer, we used a transcriptomic and proteomic approach analyzing malignant DU145, LNCaP, PC3, and benign RWPE-1 prostate cell line models transiently transfected with in vitro transcribed nc886 or antisense oligonucleotides. Multiomics revelead a significant enrichment of immune system-related pathways across the cell lines, including cytokines and interferon signaling. The interferon response provoked by nc886 was validated by functional assays. The invariability of PKR phosphorylation and NF-κB activity in the gain/loss of nc886 function experiments and the positive regulation of innate immunity suggest a PKR-independent mechanism of nc886 action. Accordingly, the GSEA of the PRAD-TCGA data set revealed immune stimulation as the nc886 most associated node also in the clinical setting. Our study showed that the reduction of nc886 leads to a blunted immune response in prostate cancer.