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Long non-coding RNAs in genitourinary malignancies: a whole new world

Abstract

Long non-coding RNAs (lncRNAs) are regulators of cellular machinery that are commonly dysregulated in genitourinary malignancies. Accordingly, the investigation of lncRNAs is improving our understanding of genitourinary cancers, from development to progression and dissemination. lncRNAs are involved in major oncogenic events in genitourinary malignancies, including androgen receptor (AR) signalling in prostate cancer, hypoxia-inducible factor (HIF) pathway activation in renal cell carcinoma and invasiveness in bladder cancer, as well as multiple other proliferation and survival mechanisms. In line with their putative oncogenic roles, new lncRNA-based classifications are emerging as potent predictors of prognosis. In clinical practice, detection of oncogenic lncRNAs in serum or urine might enable early cancer detection, and lncRNAs might also be promising therapeutic targets for patients with genitourinary cancer. Furthermore, as predictors of sensitivity to anticancer treatments, lncRNAs could be integrated into future precision medicine strategies. Overall, lncRNAs are promising new candidates for molecular studies and for discovery of innovative biomarkers and are putative therapeutic targets in genitourinary oncology.

Key points

  • Long non-coding RNAs (lncRNAs) are untranslated transcripts >200 nucleotides in length with a 3D structure that enables complex interactions with DNA, mRNA and proteins.

  • lncRNAs influence cellular functions through genome-wide transcriptional regulation as well as direct interactions with proteins in diverse signalling pathways.

  • lncRNAs are frequently dysregulated in genitourinary malignancies, resulting in the promotion of multiple oncogenic mechanisms and the acquisition of therapeutic resistance.

  • The detection of tissue-specific lncRNAs in liquid biopsy samples provides opportunities to improve the early diagnosis of genitourinary malignancies.

  • lncRNA expression signatures can improve the subtyping and risk classification of genitourinary cancers and, therefore, have the potential to help refine therapeutic strategies.

  • Targeting lncRNAs using mechanisms based on RNA interference might provide new therapeutic opportunities in genitourinary malignancies.

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Nature Reviews Urology thanks I. Seim, J. Schalken and other anonymous reviewer(s) for their contribution to the peer review of this work.

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The authors contributed equally to this manuscript.

Competing interests

G.G.M. has received consultancy fees from Bristol-Myers Squibb, Pfizer, Novartis and Ipsen. R.F. has received travel grants from Novartis and Pfizer. The other authors declare no competing interests related to this work.

Correspondence to Gabriel G. Malouf.

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Fig. 1: Main mechanisms of action of lncRNAs.
Fig. 2: Overview of oncogenic mechanisms of lncRNAs in prostate cancer.
Fig. 3: Overview of oncogenic mechanisms of lncRNAs in kidney cancer.
Fig. 4: Overview of oncogenic mechanisms of lncRNAs in bladder cancer.
Fig. 5: Principles of lncRNA targeting using single-stranded oligonucleotides.