Researchers hypothesize that the prostate-specific lncRNA PCA3 has been introduced into the human genome by an ancient virus

Prostate cancer, the most frequent type of cancer in men, is surpassed only by lung cancer in causing cancer-related death. Despite major progress in defining the mutational landscape of this tumor, its etiology remains obscure. The intronic long-noncoding RNA (lncRNA) PCA3 is a specific marker of prostate cancer that acts as a trans-dominant negative oncogene to down-regulate the tumor suppressor gene PRUNE2. The unusual genomic organization and sequence of PCA3 leads us to hypothesize that it was introduced into the human genome by an as-yet undefined oncogenic virus. Researchers at the University of New Mexico School of Medicine further suggest viral infection-related mechanisms as functional in PCA3 overexpression and involved in prostate cancer initiation and/or progression. This is supported by known links between viral infections and prostate cancer, and the lack of this tumor in other mammals despite its high incidence in humans. Finally, they suggest that genomic sequence-based approaches might help us uncover the potential role of viruses in prostate cancer etiology.

Schematic view of the proposed viral etiology of prostate cancer


In the normal prostate, basal expression of PRUNE2 correlates with low PCA3 levels. In prostate cancer, a putative oncovirus could activate PCA3 expression through a direct transactivation of a cryptic, ancient virus-derived promoter, resulting in downmodulation of PRUNE2, and leading to dysregulated cell proliferation and acquisition of malignant attributes.

Teixeira AA, Marchiò S, Dias-Neto E, Nunes DN, da Silva IT, Chackerian B, Barry M, Lauer RC, Giordano RJ, Sidman RL, Wheeler CM, Cavenee WK, Pasqualini R, Arap W. (2017) Going viral? Linking the etiology of human prostate cancer to the PCA3 long noncoding RNA and oncogenic viruses. EMBO Mol Med [Epub ahead of print]. [article]

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