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Review Open Access

MicroRNAs: Novel clinical biomarkers for cancer radiotherapy (Review)

  • Authors:
    • Junseok Park
    • Mi Eun Kim
    • Jun Sik Lee
  • View Affiliations / Copyright

    Affiliations: Department of Biological Science, Immunology Research Lab, BrainKorea21‑Four Educational Research Group for Age‑Associated Disorder Control Technology, College of Natural Sciences, Chosun University, Gwangju 61452, Republic of Korea
    Copyright: © Park et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 254
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    Published online on: July 10, 2025
       https://doi.org/10.3892/mmr.2025.13619
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Abstract

MicroRNAs (miRNAs/miRs) have attracted increasing attention as biomarkers and therapeutic agents for cancer treatment, particularly in the context of radiotherapy. Originally identified >30 years ago, miRNAs are short, non‑coding RNA molecules that regulate gene expression by binding to target mRNAs. Their involvement in physiological processes such as cell cycle regulation, DNA repair, apoptosis and signal transduction makes them essential for modulating cancer cell responses to therapeutic interventions. Recent research has explained the dual role of miRNAs in tumorigenesis. Some miRNAs function as oncogenes, promoting tumor growth and resistance to treatment, while others act as tumor suppressors, enhancing radiosensitivity and promoting apoptosis in cancer cells. Because of their stability, specificity and presence in bodily fluids, miRNAs are promising non‑invasive biomarkers for the diagnosis, prognosis and monitoring of therapeutic responses in cancer. Furthermore, miRNAs such as miR‑144, miR‑200c and let‑7 have demonstrated potential in guiding radiotherapy for breast, prostate, lung and other cancers, modulating treatment outcomes by enhancing radiosensitivity or contributing to radioresistance. Despite the early challenges of miRNA‑based therapies, advancements in miRNA delivery systems, including TargomiR‑ and liposome‑based approaches, offer promising avenues for clinical applications. The present review highlights the role of miRNAs as biomarkers and modulators in cancer radiotherapy and discusses ongoing research on miRNA delivery mechanisms to improve therapeutic outcomes. Future studies are needed to address the challenges of miRNA pleiotropy and safety in clinical applications, to advance miRNA‑based interventions in precision oncology, and to enhance the efficacy of radiotherapy across various cancer types.
View Figures

Figure 1

Overview of the interaction of miRNAs
and key proteins in response to DNA damage induced by cancer
radiotherapy. (A) Proteins and miRNAs are categorized by six
distinct colors, each representing a specific cancer type.
Highlighted proteins indicate proteins directly modulated by miRNA.
Colored miRNAs are miRNAs with an indirect influence on the
targets. (B) DNA damage activates the ATM kinase, which
subsequently recruits various proteins, including KSRP and P53.
These proteins promote the upregulation of pre-miRNAs, accelerating
miRNA maturation within the cytoplasm. (C) ATM activation also
stimulates CHK1, impairing cyclin function and checkpoint
regulation. Cyclins, which are essential for proper cell cycle
progression, normally regulate checkpoint activation. However,
mutations or upregulation of cyclins in tumor cells can disrupt
these checkpoints, leading to abnormal cell cycle progression. (D)
This process occurs through the inhibition of the anti-apoptotic
gene BCL-2, which normally prevents the release of the
mitochondrial heme protein Cyto-c into the cytoplasm. Once
released, Cyto-c initiates the intrinsic apoptotic pathway,
promoting programmed cell death. (E) The PI3K/AKT pathway, a
well-known promoter of cell proliferation, is frequently
upregulated in tumor cells due to various mechanisms, leading to
uncontrolled tumor growth. The tumor suppressor PTEN acts as a
critical antagonist to the PI3K/AKT pathway, maintaining cellular
homeostasis. (F) Additionally, miR-4766-5p enhances
radiosensitivity in gastric cancer by targeting NKAP, a well-known
transcriptional repressor involved in Notch signaling and T cell
development. miR-129-5p suppresses radioresistance by inhibiting
NUSAP1. However, APC loss-of-function mutations are common in tumor
cells, resulting in uncontrolled growth. (G) Several miRNAs
directly regulate genes and proteins associated with transcription
and angiogenesis, impacting tumor development. miR/miRNA, microRNA;
P, phosphorylated.
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Spandidos Publications style
Park J, Kim ME and Lee JS: MicroRNAs: Novel clinical biomarkers for cancer radiotherapy (Review). Mol Med Rep 32: 254, 2025.
APA
Park, J., Kim, M.E., & Lee, J.S. (2025). MicroRNAs: Novel clinical biomarkers for cancer radiotherapy (Review). Molecular Medicine Reports, 32, 254. https://doi.org/10.3892/mmr.2025.13619
MLA
Park, J., Kim, M. E., Lee, J. S."MicroRNAs: Novel clinical biomarkers for cancer radiotherapy (Review)". Molecular Medicine Reports 32.3 (2025): 254.
Chicago
Park, J., Kim, M. E., Lee, J. S."MicroRNAs: Novel clinical biomarkers for cancer radiotherapy (Review)". Molecular Medicine Reports 32, no. 3 (2025): 254. https://doi.org/10.3892/mmr.2025.13619
Copy and paste a formatted citation
x
Spandidos Publications style
Park J, Kim ME and Lee JS: MicroRNAs: Novel clinical biomarkers for cancer radiotherapy (Review). Mol Med Rep 32: 254, 2025.
APA
Park, J., Kim, M.E., & Lee, J.S. (2025). MicroRNAs: Novel clinical biomarkers for cancer radiotherapy (Review). Molecular Medicine Reports, 32, 254. https://doi.org/10.3892/mmr.2025.13619
MLA
Park, J., Kim, M. E., Lee, J. S."MicroRNAs: Novel clinical biomarkers for cancer radiotherapy (Review)". Molecular Medicine Reports 32.3 (2025): 254.
Chicago
Park, J., Kim, M. E., Lee, J. S."MicroRNAs: Novel clinical biomarkers for cancer radiotherapy (Review)". Molecular Medicine Reports 32, no. 3 (2025): 254. https://doi.org/10.3892/mmr.2025.13619
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