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Review Open Access

MicroRNA‑21: A potential therapeutic target in lung cancer (Review)

  • Authors:
    • Zhouqiang Li
    • Hualing Zhang
    • Zeshan Chen
    • Guanzhu Wu
    • Weixing Guo
    • Yun Li
  • View Affiliations / Copyright

    Affiliations: Second Ward, Department of Respiratory and Critical Care Medicine, Liuzhou Hospital of Traditional Chinese Medicine, Liuzhou, Guangxi 545000, P.R. China, Department of Traditional Chinese Medicine, Guangxi Zhuang Autonomous Region People's Hospital, Nanning, Guangxi 530016, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 67
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    Published online on: July 9, 2025
       https://doi.org/10.3892/ijo.2025.5773
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Abstract

In this review, the role of microRNA‑21 (miRNA‑21) as an oncogene in lung cancer was investigated. Studies have shown that miRNA‑21 can promote the progression of lung cancer by targeting downstream target genes, and its expression can be modulated by transcription factors, DNA methylation or competitive endogenous RNA as an upstream regulator. This review highlights that miRNA‑21 can promote the progression of lung cancer through multiple signaling pathways, with a focus on the PI3K/AKT, MEK/ERK, TGF‑β/SMAD, Hippo, NF‑κB and STAT3 signaling pathways. Mechanistically, miRNA‑21 plays an important role in the progression of lung cancer by regulating multiple biological processes, such as proliferation, invasion, metastasis, apoptosis and angiogenesis in lung cancer cells. Higher expression of miRNA‑21 is associated with chemotherapy, radiotherapy and immune resistance in lung cancer. Targeting these molecular pathways may be a novel therapeutic strategy for treating lung cancer. Additionally, miRNA‑21 can serve as a biomarker for lung cancer diagnosis, prognosis and treatment response. This review also summarized the following: i) Current methods employed to inhibit the expression of miRNA‑21 in lung cancer, including CRISPR/Cas9 technology; ii) the application of natural anticancer agents, oligonucleotides, small molecules and miRNA sponges; and iii) the nano‑delivery systems developed for miRNA‑21 inhibitors. Finally, the advancements in research on miRNA mimics and inhibitors in clinical trials, which may promote the application of miRNA‑21 in clinical trials in lung cancer, were discussed. Given that lung cancer is a considerable public health challenge, these studies provide new ways of treating patients with lung cancer.
View Figures

Figure 1

Biosynthesis and regulation of the
expression of miRNA-21. First, in the nucleus, the miRNA-21 gene is
transcribed into pri-miRNA-21 in response to RNA Pol II.
Pri-miRNA-21 is further processed into Pre-miRNA-21 via the Drosha
enzyme-Dgcr8 complex. Pre-miRNA-21 is transported to the cytoplasm
by Exportin-5. In the cytoplasm, Pre-miRNA-21 is discern and
cleaved by the TRBP and Dicer enzyme into mature double-stranded
miRNA-21, which is ~22 nucleotides in length. One strand (the guide
strand) in the mature double-stranded miRNA-21 is subsequently
loaded into the Argonaute protein to form an RISC that binds to the
3′-UTR of the target gene mRNA through sequence complementation.
The target gene mRNA degrades if perfectly bound, whereas
translational repression occurs if it is bound imperfectly.
Pri-miRNA-21, primary microRNA-21; Pre-miRNA-21, precursor
miRNA-21; RISC, RNA-induced silencing complex; RNA Pol, RNA
polymerase; TRBP, trans-activation response RNA-binding
protein.

Figure 2

MiRNA-21 targets downstream target
genes to regulate PI3K/AKT, MEK/ERK, TGF-β/SMAD, Hippo, NF-κB and
STAT3 pathways, which in turn promote the progression of lung
cancer. MiRNA-21, microRNA-21. PTEN, phosphatase and tensin
homolog; ASPP2, apoptosis stimulating protein 2 of p53; PDCD4,
programmed cell death factor 4; SMAD7, Sma and Mad-related protein
7; KIBRA, kidney and brain expressed protein.

Figure 3

MiRNA-21 can promote lung cancer
progression by directly targeting downstream target genes. However,
miRNA-21 is regulated by a variety of lncRNAs and circRNAs that
affect the expression of miRNA-21 or downstream target genes, which
in turn regulates lung cancer progression. MiRNA-21, microRNA-21;
circRNA, circular RNA; lncRNA, long non-coding RNA. LncRNA CASC2,
lncRNA cancer susceptibility candidate 2; lncRNA PLAC2, lncRNA
cancer susceptibility candidate 2; lncRNA GAS5, lncRNA growth
arrest-specific transcript 5; LncRNA Erbb4-IR, LncRNA Erb-B2
receptor tyrosine kinase 4 IR; lncRNA ASBEL, lncRNA anti-sense
transcript of BTG3 (B-cell translocation gene 3); PTEN, phosphatase
and tensin homolog; RECK, reversion inducing cysteine rich protein
with kazal motifs; IRF1, interferon-regulatory factors 1; HMSH2,
human mutS homolog 2; ADSL, adenylosuccinate lyase; PDCD4,
programmed cell death factor 4; LZTFL1, leucine zipper
transcription factor-like 1; ASPP2, apoptosis stimulating protein 2
of p53.
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Spandidos Publications style
Li Z, Zhang H, Chen Z, Wu G, Guo W and Li Y: MicroRNA‑21: A potential therapeutic target in lung cancer (Review). Int J Oncol 67: 67, 2025.
APA
Li, Z., Zhang, H., Chen, Z., Wu, G., Guo, W., & Li, Y. (2025). MicroRNA‑21: A potential therapeutic target in lung cancer (Review). International Journal of Oncology, 67, 67. https://doi.org/10.3892/ijo.2025.5773
MLA
Li, Z., Zhang, H., Chen, Z., Wu, G., Guo, W., Li, Y."MicroRNA‑21: A potential therapeutic target in lung cancer (Review)". International Journal of Oncology 67.2 (2025): 67.
Chicago
Li, Z., Zhang, H., Chen, Z., Wu, G., Guo, W., Li, Y."MicroRNA‑21: A potential therapeutic target in lung cancer (Review)". International Journal of Oncology 67, no. 2 (2025): 67. https://doi.org/10.3892/ijo.2025.5773
Copy and paste a formatted citation
x
Spandidos Publications style
Li Z, Zhang H, Chen Z, Wu G, Guo W and Li Y: MicroRNA‑21: A potential therapeutic target in lung cancer (Review). Int J Oncol 67: 67, 2025.
APA
Li, Z., Zhang, H., Chen, Z., Wu, G., Guo, W., & Li, Y. (2025). MicroRNA‑21: A potential therapeutic target in lung cancer (Review). International Journal of Oncology, 67, 67. https://doi.org/10.3892/ijo.2025.5773
MLA
Li, Z., Zhang, H., Chen, Z., Wu, G., Guo, W., Li, Y."MicroRNA‑21: A potential therapeutic target in lung cancer (Review)". International Journal of Oncology 67.2 (2025): 67.
Chicago
Li, Z., Zhang, H., Chen, Z., Wu, G., Guo, W., Li, Y."MicroRNA‑21: A potential therapeutic target in lung cancer (Review)". International Journal of Oncology 67, no. 2 (2025): 67. https://doi.org/10.3892/ijo.2025.5773
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