Lung cancer (LC) is a major global health issue, with high mortality rates and limited therapeutic options. It is primarily categorized into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Despite significant advancements in diagnostic techniques, LC remains highly lethal, largely due to late-stage diagnosis and aggressive metastasis. Recent research has emphasized the pivotal role of microRNAs (miRNAs) in the pathogenesis of LC. These small, non-coding RNA molecules regulate gene expression by binding to messenger RNA (mRNA), leading to translation inhibition or degradation. This review focuses on the oncogenic potential of miRNAs in LC, their dysregulation, functional roles, and their potential implications for both diagnosis and therapy.
Role of MicroRNAs in Lung Cancer
miRNAs play essential roles in various aspects of cancer biology, including tumor initiation, progression, and metastasis. Dysregulation of miRNAs in LC often leads to altered regulation of critical tumor-suppressor genes and oncogenes. For instance, oncogenic miRNAs like miR-21, miR-9-5p, and miR-31 have been found to promote tumor cell proliferation, migration, and resistance to chemotherapy by targeting tumor suppressor genes. miR-21, in particular, is upregulated in several cancers, including LC, and promotes cell proliferation and inhibits apoptosis, contributing to a more aggressive tumor phenotype.
miRNA Biogenesis and Dysregulation in LC
The biogenesis of miRNAs is a complex process involving transcription, processing, and maturation. Any dysregulation at any stage of this process can lead to aberrant miRNA expression, which is often observed in cancer cells. In LC, miRNA dysregulation contributes to tumorigenesis by targeting various genes involved in cell cycle regulation, apoptosis, angiogenesis, and metastasis. The canonical miRNA biogenesis pathway involves transcription of miRNA genes by RNA polymerase II, followed by processing by enzymes like Drosha and Dicer. Recent findings also suggest that exosomal miRNAs play a crucial role in modifying the tumor microenvironment, influencing cancer progression, and resistance to treatment.
Oncogenic and Tumor Suppressor miRNAs in LC
miRNAs can act as either oncogenes or tumor suppressors in LC. Oncogenic miRNAs promote tumor progression by targeting genes that regulate cell growth, apoptosis, and migration. For example, miR-155 and miR-10b have been shown to enhance LC cell growth, migration, and invasion, contributing to poor prognosis in patients. Conversely, tumor-suppressive miRNAs, such as miR-1 and miR-7, inhibit tumor growth by targeting oncogenic pathways. However, the expression of these tumor-suppressive miRNAs is frequently downregulated in LC, leading to the activation of oncogenic pathways.
Therapeutic Potential and Clinical Implications
The dysregulation of miRNAs presents both challenges and opportunities for LC diagnosis and therapy. Oncogenic miRNAs could be targeted therapeutically using miRNA inhibitors or antagomirs, which block their function. Conversely, restoring the expression of tumor-suppressive miRNAs could also offer therapeutic benefits. miRNAs have shown potential as non-invasive biomarkers for early detection of LC, with circulating miRNAs in blood or exosomes offering a promising approach for monitoring disease progression and response to treatment. The ability to target specific miRNAs also opens avenues for personalized cancer therapy, tailoring treatments based on the unique miRNA profiles of individual patients.
Conclusion
miRNAs are crucial regulators in lung cancer biology and provide valuable insights into the molecular mechanisms underlying the disease. Oncogenic miRNAs contribute to tumor growth, metastasis, and chemotherapy resistance, while tumor-suppressive miRNAs act as negative regulators of these processes. Targeting miRNAs holds significant promise for both diagnostic and therapeutic applications in LC. However, further research is needed to fully understand the complex miRNA regulatory networks and their interactions with other signaling pathways. Advances in miRNA-based therapies and their integration into clinical practice may pave the way for more effective and personalized treatment strategies for lung cancer.
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The study was recently published in the Cancer Screening and Prevention .
Cancer Screening and Prevention (CSP) publishes high-quality research and review articles related to cancer screening and prevention. It aims to provide a platform for studies that develop innovative and creative strategies and precise models for screening, early detection, and prevention of various cancers. Studies on the integration of precision cancer prevention multiomics where cancer screening, early detection and prevention regimens can precisely reflect the risk of cancer from dissected genomic and environmental parameters are particularly welcome.
