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.
Authors
- Ana Julia Fernández-Álvarez (ORCID: https://orcid.org/0000-0002-5296-5678)
- Yong Sun Lee
- Stanley K. Liu (ORCID: https://orcid.org/0000-0001-6851-0857)
- Vladimir Ignatchenko (ORCID: https://orcid.org/0009-0007-7457-7274)
- Thomas Kislinger (ORCID: https://orcid.org/0000-0003-3525-5540)
- Rafael Sebastián Fort (ORCID: https://orcid.org/0000-0002-0161-8860)
- Graciela L. Boccaccio (ORCID: https://orcid.org/0000-0003-1349-898X)
- Marı́a Ana Duhagon (ORCID: https://orcid.org/0000-0001-6468-1704)
- Chiara Colantuono (ORCID: https://orcid.org/0000-0003-3014-6978)
- José Roberto Sotelo-Silveira (ORCID: https://orcid.org/0000-0002-4758-8556)
- Beatríz Garat (ORCID: https://orcid.org/0000-0003-2679-8244)
- Carolina Oliveira‐Rizzo (ORCID: https://orcid.org/0000-0003-3141-7397)
- Shahbaz Khan
Institutions
- Sunnybrook Health Science Centre (CA)
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- Universidad de la República de Uruguay (UY)
- University of Toronto (CA)
- Universidad de Buenos Aires (AR)
- Fundación Instituto Leloir (AR)
- Princess Margaret Cancer Centre (CA)
- National Cancer Center (US)
- National Cancer Center (KR)
- Instituto de Investigaciones Biológicas Clemente Estable (UY)
- Fundación Ciencias Exactas y Naturales (AR)
Publication Details
- Journal
- Journal of Proteome Research
- Published
- 2024-12-26
- DOI
- https://doi.org/10.1021/acs.jproteome.4c00521
- Citations
- 3
- Primary Topic
- Cancer-related molecular mechanisms research
- Type
- article
- Field-Weighted Citation Impact
- 0.86
Funders
- Agencia Nacional de Investigación e Innovación
- Universidad de la República Uruguay
- Comisión Sectorial de Investigación Científica