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Review Open Access

Analysis of the role of RNA regulatory networks in cancer treatment: Mechanisms, applications and future prospects (Review)

  • Authors:
    • Wenhua Ren
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    Affiliations: College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu 210023, P.R. China
    Copyright: © Ren et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 114
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    Published online on: October 22, 2025
       https://doi.org/10.3892/mco.2025.2909
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Abstract

RNA regulatory networks play a central role in cancer development and progression, influencing key biological processes such as cell cycle control, proliferation, apoptosis and tumor microenvironment interactions. MicroRNA (miR) variants, specifically isomiRs, have emerged as a novel research focus due to their altered target specificity and cancer‑specific expression patterns, highlighting their potential as diagnostic markers and therapeutic targets. Additionally, advanced technologies such as single‑cell sequencing and CRISPR screening offer novel avenues to dissect the complexity of RNA networks and identify key regulators for personalized therapy. The present review provides an integrative overview of RNA regulatory mechanisms, with a particular focus on the functional dynamics of isomiRs and competing endogenous RNA networks. Finally, the translational potential of isomiRs in precision oncology is described and key challenges and future directions in the field are outlined.
View Figures

Figure 1

Core components of RNA regulatory
networks in cancer. miRNAs and isomiRs bind to the RISC, which
guides them to complementary mRNA targets. This interaction results
in either translational repression or mRNA degradation. lncRNAs act
as miRNA sponges, and RNA species can be exported via exosomes for
intercellular communication. RISC, RNA-induced silencing complex;
miRNA, microRNA; isomiR, microRNA isoform; mRNA, messenger RNA;
lncRNA, long non-coding RNA.

Figure 2

Functional impact of 5'-isomiRs in
tumorigenesis. The 5'-end variation shifts the miRNA seed,
retargeting transcripts. Heatmap shows z-scored log2(RPM+1) of
representative 5’-isomiRs in TCGA BRCA, COAD/READ and LIHC
(cancer-type-specific). IsomiR, microRNA isoform; miRNA, microRNA;
TCGA, The Cancer Genome Atlas; BRCA, breast invasive carcinoma;
COAD/READ, colon/rectum adenocarcinoma; LIHC, liver hepatocellular
carcinoma.

Figure 3

Integrated mechanisms of RNA
regulatory networks in tumor immune modulation. (A) ceRNA networks:
lncRNAs act as miRNA sponges, upregulating immune checkpoint genes
such as PD-L1 and TGF-β. (B) isomiRs redirect gene targeting
through altered seed sequences, promoting immune evasion. (C)
Exosomal lncRNAs regulate immune cell activity in the TME. ceRNA,
competitive endogenous RNA; lncRNA, long non-coding RNA; miRNA,
microRNA; PD-L1, programmed death-ligand 1; TGF-β, transforming
growth factor-β; TME, tumor microenvironment.

Figure 4

Single-cell multi-omics integration
to resolve cell type-specific RNA interaction networks. scRNA-seq
and scATAC-seq are jointly embedded to define cell types (colored
clusters). Peak-gene links and TF regulons are derived from
chromatin accessibility and motif/footprint analysis, while
microRNA/isomiR constraints (seed/MRE) restrict candidate edges.
Optional spatial data prioritize edges co-localized in the TME.
Output: Cell type-resolved ceRNA/isomiR networks and prioritized
targets. scRNA-seq, single-cell RNA sequencing; scATAC-seq,
single-cell assay for transposase-accessible chromatin; isomiR,
microRNA isoform; MRE, microRNA response element; TME, tumor
microenvironment; ceRNA, competitive endogenous RNA; TF,
transcription factor.

Figure 5

Translational constraints for RNA
therapeutics. Schematic overview of delivery (LNP with ligand and
tumor entry), innate immunity (endosomal TLR7/8 sensing and
mitigation by chemical modifications) and off-target control (seed
motif, AGO engagement and mRNA ladder), converging on safer dosing
and robust target validation. LNP, lipid nanoparticle; TLR,
Toll-like receptor; mRNA, messenger RNA; AGO, Argonaute.
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Copy and paste a formatted citation
Spandidos Publications style
Ren W: Analysis of the role of RNA regulatory networks in cancer treatment: Mechanisms, applications and future prospects (Review). Mol Clin Oncol 23: 114, 2025.
APA
Ren, W. (2025). Analysis of the role of RNA regulatory networks in cancer treatment: Mechanisms, applications and future prospects (Review). Molecular and Clinical Oncology, 23, 114. https://doi.org/10.3892/mco.2025.2909
MLA
Ren, W."Analysis of the role of RNA regulatory networks in cancer treatment: Mechanisms, applications and future prospects (Review)". Molecular and Clinical Oncology 23.6 (2025): 114.
Chicago
Ren, W."Analysis of the role of RNA regulatory networks in cancer treatment: Mechanisms, applications and future prospects (Review)". Molecular and Clinical Oncology 23, no. 6 (2025): 114. https://doi.org/10.3892/mco.2025.2909
Copy and paste a formatted citation
x
Spandidos Publications style
Ren W: Analysis of the role of RNA regulatory networks in cancer treatment: Mechanisms, applications and future prospects (Review). Mol Clin Oncol 23: 114, 2025.
APA
Ren, W. (2025). Analysis of the role of RNA regulatory networks in cancer treatment: Mechanisms, applications and future prospects (Review). Molecular and Clinical Oncology, 23, 114. https://doi.org/10.3892/mco.2025.2909
MLA
Ren, W."Analysis of the role of RNA regulatory networks in cancer treatment: Mechanisms, applications and future prospects (Review)". Molecular and Clinical Oncology 23.6 (2025): 114.
Chicago
Ren, W."Analysis of the role of RNA regulatory networks in cancer treatment: Mechanisms, applications and future prospects (Review)". Molecular and Clinical Oncology 23, no. 6 (2025): 114. https://doi.org/10.3892/mco.2025.2909
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