Page 60 - TD-3-4

Tumor Discovery

REVIEW ARTICLE
Targeting the interplay between biomolecular

condensates and regulatory RNAs in cancer

1
Palmiro Poltronieri * and Sudipta Joardar 2
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

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.
*Corresponding author:
Palmiro Poltronieri Epitranscriptome-modifying enzymes regulate the stability and oncogenic
(palmiro.poltronieri@ispa.cnr.it) potential of noncoding RNAs (ncRNAs). These RNAs, along with their associated
epitranscriptomic and protein modifications, play critical roles in the functioning and
Citation: Poltronieri P, Joardar S.
Targeting the interplay between dissolution of condensates. Recent advancements in cancer therapy have focused on
biomolecular condensates and developing drugs targeting the epitranscriptomic machinery, including the writers,
regulatory RNAs in cancer. Tumor readers, and erasers of RNA modifications. Therapeutic strategies aim to target
Discov. 2024;3(4):4657.
doi: 10.36922/td.4657 oncogenic RNAs, tumor-promoting proteins, and RNA–protein interaction domains.
Several cancer therapeutic compounds have been developed using the PROTAC and
Received: August 26, 2024
RIBOTAC approaches. Moreover, small molecules targeting protein–RNA interactions
Accepted: October 25, 2024 and antisense oligonucleotides have been developed. Promising avenues in cancer
Published Online: December 6, therapeutics involve the inhibition of ncRNAs and their associated protein complexes,
2024 modulation of BCs, regulation of SGs and paraspeckles, and development of small
Copyright: © 2024 Author(s). molecule compounds with potential applications across various cancer types.
This is an Open-Access article
distributed under the terms of the
Creative Commons Attribution Keywords: Biomolecular condensates; Noncoding RNAs; RNA–protein interactions;
License, permitting distribution, Therapeutic targets; Cancer; Epitranscriptomics; Epigenetics
and reproduction in any medium,
provided the original work is
properly cited.
Publisher’s Note: AccScience
Publishing remains neutral with 1. Introduction
regard to jurisdictional claims in
published maps and institutional Biomolecular condensates (BCs) are membraneless organelles (MLOs) that are crucial
affiliations. for intricate cellular biochemical reactions. Condensates within the nucleus include the

Volume 3 Issue 4 (2024) 1 doi: 10.36922/td.4657