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MicroRNA‑21: A potential therapeutic target in lung cancer (Review)
Zhouqiang Li1, Hualing Zhang1, Zeshan Chen2
1Second Ward, Department of Respiratory and Critical Care Medicine, Liuzhou Hospital of Traditional Chinese Medicine, Liuzhou, Guangxi 545000, P.R. China.
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.
Insights
MicroRNA-21 (miRNA-21) drives lung cancer progression by affecting key pathways and biological processes. Inhibiting miRNA-21 offers a promising therapeutic strategy and diagnostic biomarker for lung cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Lung cancer remains a leading cause of cancer-related mortality worldwide.
- MicroRNA-21 (miRNA-21) has emerged as a significant oncogene in various cancers, including lung cancer.
- Understanding miRNA-21's regulatory mechanisms and downstream effects is crucial for developing effective lung cancer therapies.
Purpose of the Study:
- To review the multifaceted role of miRNA-21 as an oncogene in lung cancer.
- To elucidate the signaling pathways and biological processes regulated by miRNA-21 in lung cancer progression.
- To explore therapeutic strategies and diagnostic applications of targeting miRNA-21.
Main Methods:
- Comprehensive literature review of studies investigating miRNA-21 in lung cancer.
- Analysis of miRNA-21's regulatory mechanisms, including upstream regulators and downstream targets.
- Examination of miRNA-21's involvement in key signaling pathways (PI3K/AKT, MEK/ERK, TGF-β/SMAD, Hippo, NF-κB, STAT3).
- Review of therapeutic approaches targeting miRNA-21, including CRISPR/Cas9, natural agents, oligonucleotides, miRNA sponges, and nano-delivery systems.
- Assessment of miRNA-21's potential as a biomarker for diagnosis, prognosis, and treatment response.
Main Results:
- miRNA-21 promotes lung cancer progression by targeting downstream genes and regulating proliferation, invasion, metastasis, apoptosis, and angiogenesis.
- Its expression is modulated by transcription factors, DNA methylation, and competitive endogenous RNAs.
- Higher miRNA-21 expression correlates with resistance to chemotherapy, radiotherapy, and immunotherapy.
- Various methods to inhibit miRNA-21, including CRISPR/Cas9 technology and miRNA sponges, have been developed.
- Nano-delivery systems enhance the efficacy of miRNA-21 inhibitors.
Conclusions:
- miRNA-21 is a critical oncogene in lung cancer, driving tumor progression through multiple signaling pathways.
- Targeting miRNA-21 and its associated pathways presents a novel therapeutic strategy for lung cancer.
- miRNA-21 holds significant potential as a biomarker for lung cancer diagnosis, prognosis, and predicting treatment response.
- Advancements in miRNA-21 inhibitors and their clinical trial applications offer new hope for lung cancer patients.
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