Therapeutic Targeting of MicroRNAs in Human Cancer

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell and Gene Therapy".

Deadline for manuscript submissions: closed (31 March 2026) | Viewed by 1662

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Guest Editor
The Wistar Institute, Molecular & Cellular Oncogenesis Program, Philadelphia, PA, USA
Interests: non-coding RNA; cancer therapy
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Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute to our upcoming Special Issue, entitled “Therapeutic Targeting of MicroRNAs in Human Cancer.” As our knowledge of microRNAs (miRNAs) continues to expand, new research has revealed their profound and context-dependent roles in shaping tumor biology, therapy response, and the tumor microenvironment. In addition to their well-established influence on proliferation, apoptosis, and metastasis, miRNAs are now recognized as critical regulators of immune evasion, metabolic reprogramming, and therapeutic resistance.

This Special Issue provides an exciting opportunity to showcase original research and critical reviews that explore the next generation of miRNA-based cancer therapies. In this contribution, we aim to highlight emerging therapeutic strategies that integrate spatial biology, nanomedicine, and RNA technologies to overcome key barriers in the clinical translation of miRNA therapeutics. Areas of focus will include, but are not limited to, the following:

  • Targeted Delivery Systems: Advances in nanoparticle platforms—including lipid-based nanoparticles (LNPs), polymer conjugates, and engineered exosomes—enable a targeted and efficient delivery of miRNA mimics and inhibitors to tumors, improving their bioavailability and reducing systemic toxicity.
  • CRISPR and mRNA Technologies: Genome and transcriptome editing tools, including CRISPR-Cas systems and synthetic mRNA vectors, offer novel strategies for modulating miRNA expression with spatial and temporal control, either by editing miRNA loci or delivering pri-/pre-miRNA transcripts.
  • Spatial miRNomics and Tumor Microenvironment Profiling: The integration of spatial transcriptomics and single-exosome profiling has revealed heterogeneous miRNA expression across tumor ecosystems. This spatial information is essential for designing precision-targeted miRNA interventions adapted to the local microenvironment.
  • Combination Therapeutic Strategies: miRNA-based approaches hold promise in enhancing the efficacy of existing treatments. Combination therapies involving miRNA mimics or inhibitors alongside immunotherapy, chemotherapy, or metabolic pathway modulators are being actively explored to reverse resistance mechanisms and improve patient outcomes.
  • Therapeutic Candidates and Translation: The development and preclinical evaluation of key miRNA candidates—including miR-122, miR-15/16, miR-34a, etc.—illustrate both the promise and the challenges of bringing miRNA therapeutics closer to clinical application.

By bringing together interdisciplinary insights and state-of-the-art advances, this contribution aims to enrich the ongoing scientific dialogue and support the rational development of miRNA-targeted therapies. We hope that the papers submitted to this Special Issue will offer new data, deepen our mechanistic understanding, and collectively push the field toward more effective, personalized cancer treatments.

We look forward to the submission of high-quality original articles and comprehensive reviews that expand the frontiers of miRNA-based therapeutic strategies in cancer. Together, through the insights and innovations shared across this issue, we aim to accelerate progress in the translation of miRNA science into clinical impact.

Dr. Behzad Mansoori
Guest Editor

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Keywords

  • microRNAs
  • nanoparticle platforms
  • spatial miRNomics
  • combination therapeutic strategies

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Published Papers (1 paper)

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Review

34 pages, 2799 KB  
Review
MicroRNAs in Prostate Cancer Liquid Biopsies: Early Detection, Prognosis, and Treatment Monitoring
by Seyyed Mohammad Yaghoubi, Erfan Zare, Sina Jafari Dargahlou, Maryam Jafari, Mahdiye Azimi, Maedeh Khoshnazar, Solmaz Shirjang and Behzad Mansoori
Cells 2026, 15(1), 83; https://doi.org/10.3390/cells15010083 - 4 Jan 2026
Cited by 1 | Viewed by 1232
Abstract
Prostate cancer (PCa) is a common malignancy in men worldwide, with incidence projected to rise in the coming years. Traditional screening and diagnostic methods, such as prostate-specific antigen (PSA) testing and biopsy, face limitations in specificity and invasiveness. Circulating microRNAs (miRNAs) have emerged [...] Read more.
Prostate cancer (PCa) is a common malignancy in men worldwide, with incidence projected to rise in the coming years. Traditional screening and diagnostic methods, such as prostate-specific antigen (PSA) testing and biopsy, face limitations in specificity and invasiveness. Circulating microRNAs (miRNAs) have emerged as stable, non-invasive biomarkers obtainable via liquid biopsies (blood, urine, semen) that could transform PCa management. These small regulatory RNAs reflect underlying tumor biology and are detectable at early disease stages, enabling improved early detection when used alongside or in place of PSA. Distinct miRNA expression patterns correlate with tumor aggressiveness. For example, miR-141 and miR-375 are elevated in metastatic cases, whereas let-7 family members and miR-326 are upregulated in aggressive disease, highlighting their prognostic value. Moreover, dynamic changes in reported miRNAs during therapy provide real-time insights into treatment response. In androgen-deprivation therapy (ADT), oncogenic miRNAs, such as miR-21 and miR-125b, increase upon resistance, whereas a decline in tumor-suppressive miRNAs, such as miR-23b/-27b, flags the transition to castration-resistant PCa (CRPC). Similarly, baseline levels of miRNAs (e.g., miR-200b/c, miR-20a) can predict chemotherapy outcomes. Integrating multi-miRNA panels has demonstrated superior accuracy for risk stratification and monitoring, paving the way for personalized treatment. Although promising, clinical implementation of miRNA-based assays requires further validation, standardization of protocols, and large-scale prospective studies. Harnessing circulating miRNAs could usher in a new era of precision oncology for PCa, improving early diagnosis, prognostication, and real-time therapeutic guidance. Full article
(This article belongs to the Special Issue Therapeutic Targeting of MicroRNAs in Human Cancer)
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