AccScience Publishing / TD / Volume 3 / Issue 4 / DOI: 10.36922/td.4657
REVIEW ARTICLE

Targeting the interplay between biomolecular condensates and regulatory RNAs in cancer

Palmiro Poltronieri1* Sudipta Joardar2
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1 National Research Council of Italy, Department of Agrofood, Institute of Sciences of Food Productions, CNR-ISPA, Lecce, Apulia, Italy
2 Autonomous University of Barcelona, Center for Research in Agricultural Genomics, Cerdanyola Del Valles, Barcelona, Spain
Tumor Discovery 2024, 3(4), 4657 https://doi.org/10.36922/td.4657
Submitted: 26 August 2024 | Accepted: 25 October 2024 | Published: 6 December 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Biomolecular condensates (BCs), RNA–protein complexes, have emerged as potential therapeutic targets for various cellular pathologies, including cancer. The mechanisms underlying liquid–liquid phase separation rely on the properties of proteins with intrinsically disordered regions and prion-like domains, which drive phase separation in conjunction with their RNA partners. These ribonucleoprotein complexes are distinct in their localization, compartmentalization, epigenetic regulation, and dynamics. BCs are categorized as either nuclear—such as promyelocytic leukemia nuclear bodies, speckles, paraspeckles, and Cajal bodies—or cytosolic, including stress granules (SGs), P bodies, and U bodies. Regulatory RNAs, assembled with protein partners through phase separation, exhibit oncogenic properties and perform key biological functions, including gene transcription, euchromatin/heterochromatin formation, mRNA splicing, mRNA translation, protein compartmentalization, and degradation. Epitranscriptome-modifying enzymes regulate the stability and oncogenic potential of noncoding RNAs (ncRNAs). These RNAs, along with their associated epitranscriptomic and protein modifications, play critical roles in the functioning and dissolution of condensates. Recent advancements in cancer therapy have focused on developing drugs targeting the epitranscriptomic machinery, including the writers, readers, and erasers of RNA modifications. Therapeutic strategies aim to target oncogenic RNAs, tumor-promoting proteins, and RNA–protein interaction domains. Several cancer therapeutic compounds have been developed using the PROTAC and RIBOTAC approaches. Moreover, small molecules targeting protein–RNA interactions and antisense oligonucleotides have been developed. Promising avenues in cancer therapeutics involve the inhibition of ncRNAs and their associated protein complexes, modulation of BCs, regulation of SGs and paraspeckles, and development of small molecule compounds with potential applications across various cancer types.

Keywords
Biomolecular condensates
Noncoding RNAs
RNA–protein interactions
Therapeutic targets
Cancer
Epitranscriptomics
Epigenetics
Funding
None.
Conflict of interest
The authors declare that they have no competing interests.
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Tumor Discovery, Electronic ISSN: 2810-9775 Print ISSN: 3060-8597, Published by AccScience Publishing