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LncRNAs in human cancers: signal from noise

Journal

TRENDS IN CELL BIOLOGY
Volume 32, Issue 7, Pages 565-573

Publisher

CELL PRESS
DOI: 10.1016/j.tcb.2022.01.006

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Funding

  1. Melanoma Research Alliance (MRA)
  2. Stichting Tegen Kanker [FAF-F/2018/1184]
  3. KU Leuven C1 grant [C16/19/006]

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Recent studies have shown that long noncoding RNAs play a crucial role in cancer by regulating LLPS. This discovery may lead to the development of new diagnostic tools and treatment methods.
Given the biochemical reaction stochasticity, the mechanisms leading to conservation of biological functions from noise are obscure. Pervasive transcription of nonconserved genomic regions generates lowly expressed cancer-specific long noncoding RNAs (lncRNAs). How such poorly expressed transcripts, often undetectable in normal tissues, consistently modulate the activity of multiple abundant proteins leading to cancer phenotypes is unclear. Biochemical reaction compartmentalisation in response to environmental oscillations through liquid-liquid phase separation (LLPS) may explain the emergence of order from molecular noise. LncRNAs contain repetitive sequences and as such contribute to molecular crowding and LLPS. We propose that lncRNAs mediate cancer stress signals by regulating aberrant LLPS. This emerging model and its consequences for stoichiometry and specificity may lead to the development of diagnostic tools and cancer-specific drugs.

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