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Targeting RNA to Improve Cancer Precision Medicine

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 30 September 2026 | Viewed by 708

Special Issue Editors


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Guest Editor
Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
Interests: cancer; cell death pathways; miRNA; long non-coding RNA; cell signaling; apoptosis; autophagy; nanotechnology; drug delivery; chemotherapy; combination therapy; target-therapy; immunotherapy; biomarkers
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Guest Editor
Department of Precision Medicine, University of Campania “L. Vanvitelli”, Via de Crecchio 7, 80138 Naples, Italy
Interests: cancer; non-coding RNA
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
Interests: cancer; RNA

Special Issue Information

Dear Colleagues,

RNA therapeutics are increasingly changing the standard of care for many diseases, including cancer, moving it toward personalized medicine.

RNA-based drugs have the potential to circumvent the problems that commonly affect traditional drugs acting as protein inhibitors, i.e., the lack of druggable active sites, the poor affinity and accessibility to the binding sites, and the large size of therapeutic antibodies/peptides, which results in low bioavailability and difficult cell membrane crossing.

On the other hand, therapeutic strategies based on nucleic acids are able to circumvent many of these limitations as they act at the DNA or RNA level, modulating gene expression through inhibition, addition, replacing, or editing, availing of the cellular translational machinery. Some critical points for DNA-based drugs are the permeation of two membranes to reach the nucleus and the safety concerns due to possible integration into the chromosomes. These drawbacks can be overcome by RNA therapeutics, which are introduced into the cytoplasm and do not pose a risk for the host genome.

The development of RNA drugs is rapidly evolving and encompasses different classes of therapeutics, such as antisense oligonucleotides, aptamers, siRNAs, miRNAs, and mRNA. The main advantages in the use of RNA-based drugs are represented by the simple and cost-effective production, the ability to act on “undruggable” targets, and the speed in obtaining specific constructs for customised treatments. Even this class of therapeutics still presents challenges to be addressed for successful employment in therapy, specifically the efficiency of delivery into the cytoplasm, the rapid degradation by RNases, and the possible triggering of undesirable immune system response.

The improvement and innovation of delivery strategies, mostly introducing chemical modifications on nucleic acid backbone and ribose ring, also coupled with the employment of advanced nanocarriers, represent the primary objectives of the current and future research of RNA-based drugs, which are going to find proficient application in oncology, revolutionising the gold standard for therapeutic interventions.

Dr. Gabriella Misso
Dr. Anna Grimaldi
Dr. Chiara Tammaro
Guest Editors

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Keywords

  • cancer
  • RNA therapy
  • RNA delivery
  • RNA
  • miRNA
  • mRNA
  • siRNA
  • oligonucleotides
  • aptamers
  • precision medicine

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Published Papers (1 paper)

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Review

47 pages, 3333 KB  
Review
miRNA–lncRNA Cross-Regulation Landscape in Cancer: From Molecular Mechanisms to Therapeutic and Diagnostic Applications
by Giuseppe Scafuro, Myriam Karam, Ayesha Khan, Chiara Tammaro, Takehiro Nagatsuka, Anna Grimaldi, Alessia Maria Cossu, Silvia Zappavigna, Michele Caraglia, Gabriella Misso and Michela Falco
Cancers 2026, 18(10), 1610; https://doi.org/10.3390/cancers18101610 - 15 May 2026
Abstract
Background/Objectives: Over the past two decades, non-coding RNAs (ncRNAs) have emerged as key regulators of gene expression, reshaping the classical view of the genome as predominantly protein-coding. Among them, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) play central roles in controlling gene expression [...] Read more.
Background/Objectives: Over the past two decades, non-coding RNAs (ncRNAs) have emerged as key regulators of gene expression, reshaping the classical view of the genome as predominantly protein-coding. Among them, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) play central roles in controlling gene expression at multiple levels. Rather than acting independently, these molecules form complex and interconnected regulatory networks, and their interplay appears particularly relevant in cancer. This review aims to examine the mechanisms underlying miRNA-lncRNA cross-regulation and to explore their functional and clinical implications in tumor biology. Methods: We performed a comprehensive analysis of the current literature focusing on studies investigating miRNA-lncRNA interactions in cancer. Particular attention was given to mechanistic insights, including the competing endogenous RNA (ceRNA) hypothesis, as well as alternative regulatory models involving direct RNA interactions and chromatin-associated processes. Results: miRNA-lncRNA interactions have been associated with cancer progression and therapeutic response across different tumor types, although their mechanisms are highly context-dependent. While the ceRNA hypothesis, based on competition for shared microRNA response elements (MREs), provides a useful framework, it does not fully explain all observed phenomena. Evidence shows that miRNAs can directly regulate lncRNA stability, whereas lncRNAs can influence miRNA biogenesis. Additionally, chromatin-related mechanisms suggest that these interactions extend beyond post-transcriptional regulation. These RNA networks intersect with major oncogenic pathways, including PI3K/AKT/mTOR signaling, hypoxia responses, and epigenetic regulators such as EZH2, thereby affecting key cancer processes such as proliferation, epithelial–mesenchymal transition (EMT), and metabolic reprogramming. From a clinical perspective, the stability of ncRNAs in biological fluids highlights their potential as biomarkers. Combined miRNA-lncRNA signatures may improve diagnostic and prognostic accuracy compared to single markers, although further validation is required. Therapeutic strategies targeting ncRNA networks, such as miRNA mimics, antagomiRs, and lncRNA-directed approaches, are under investigation; however, challenges related to delivery, specificity, and toxicity remain. Conclusions: miRNA-lncRNA cross-regulation represents a complex and multifaceted layer of gene regulation in cancer. A deeper understanding of these interactions could support the development of more accurate diagnostic tools and more effective RNA-based therapeutic strategies, although significant technical and biological challenges still need to be addressed. Full article
(This article belongs to the Special Issue Targeting RNA to Improve Cancer Precision Medicine)
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