Unraveling Therapeutic Opportunities and the Diagnostic Potential of microRNAs for Human Lung Cancer

Abstract

Lung cancer is a major public health problem and a leading cause of cancer-related deaths worldwide. Despite advances in treatment options, the five-year survival rate for lung cancer patients remains low, emphasizing the urgent need for innovative diagnostic and therapeutic strategies. MicroRNAs (miRNAs) have emerged as potential biomarkers and therapeutic targets for lung cancer due to their crucial roles in regulating cell proliferation, differentiation, and apoptosis. For example, miR-34a and miR-150, once delivered to lung cancer via liposomes or nanoparticles, can inhibit tumor growth by downregulating critical cancer promoting genes. Conversely, miR-21 and miR-155, frequently overexpressed in lung cancer, are associated with increased cell proliferation, invasion, and chemotherapy resistance. In this review, we summarize the current knowledge of the roles of miRNAs in lung carcinogenesis, especially those induced by exposure to environmental pollutants, namely, arsenic and benzopyrene, which account for up to 1/10 of lung cancer cases. We then discuss the recent advances in miRNA-based cancer therapeutics and diagnostics. Such information will provide new insights into lung cancer pathogenesis and innovative diagnostic and therapeutic modalities based on miRNAs.

Keywords: delivery; diagnosis; environmental carcinogens; lung cancer; microRNAs; therapeutics.

Figure 1

Representative diagrams of the causative factors of lung carcinogenesis and influence of miRNAs on lung cancer development. (A) A visual representation that shows how genetic and environmental factors come together to cause lung cancer. (B) A graphical portrayal of miRNAs with their different modulatory functions in lung cancer.

Figure 2

Representative diagrams of the miRNAs that have been associated with human lung cancer and their corresponding targets. (A) The implicated miRNAs in human lung cancer progression; those labeled in blue are involved in lung cancer induced by arsenic and BaP exposure. (B) The shared miRNAs that play a role in lung cancer and are also involved in the development of lung cancer caused by exposure to arsenic and BaP. (C) The target genes responsible for the progression of lung cancer and those that are also responsible for the development of lung cancer triggered by exposure to arsenic and BaP. (D) Representative diagram for miRNAs and their gene targets in lung cancer tissue. The miRNAs linked to lung cancer are depicted in red, whereas those associated with lung cancer induced by arsenic and BaP are indicated in blue. The genes that are targeted by these miRNAs are visually represented in green.

Figure 3

Illustrating network of the signaling mechanisms in lung cancer through miRNA-mediated regulation. The image shows the signaling pathways that are involved in lung cancer, including Wnt, TGF-β, Notch, Hedgehog, PI3K/Akt, MAPK/ERK, JAK/STAT, NF-κB, Hippo, and Tp53. Each of these signaling pathways is regulated by many miRNAs. Four specific miRNAs, namely miR-21, miR-150, miR-155, and miR-34, are known to have a significant impact on the regulation and progression of lung cancer, and they will be focused on by miRNA therapeutics.

Figure 4

A detailed model illustrating the biogenesis of miRNAs and demonstrating the effectiveness of miRNA-based therapies for managing lung metastases. (A) The biogenesis of miRNAs involves transcription by RNA polymerase II, processing by Drosha and Dicer enzymes, and incorporation into the RNA-induced silencing complex (RISC) to regulate gene expression at both the cellular and animal levels through oncology-directed miRNA replacement therapy. (B) Experimental animals have been used to test the efficacy of miRNA-based treatments in restricting metastasis, with studies conducted to assess the ability of these therapies to prevent the spread of cancer to other parts of the body.

Figure 5

An illustrated guide to the diagnostic and therapeutic potential of miRNAs and methods for delivering miRNA therapeutics. MiRNAs can be extracted from circulating miRNAs, circulating tumor cells, primary tumor cells, and tumor lung tissue and analyzed for their expression patterns. These miRNA profiles can then be used to develop non-invasive diagnostic tools for cancer detection and monitoring and to guide personalized treatment strategies. The delivery methods include lipid-based nanoparticles, viral vectors, exosomes, aptamers, peptide-based delivery, and electroporation. Each method has its own advantages and limitations, and the choice of delivery method depends on factors such as the type of miRNA therapeutic and the target tissue.