MicroRNAs as Targets for Lung Cancer

miRNA therapeutics face numerous challenges including targeted delivery, specificity, stability, immune response, and toxicity. Overcoming these challenges is paramount for success.

Written by
Anna Tzani
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  • Target Selection
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The Promise of MicroRNAs

MicroRNAs (miRNAs) are small RNA molecules that play a crucial role in regulating gene expression by binding to target mRNA. Their dysregulation has been implicated in various cancers, including lung cancer.1 These discoveries have resulted in the development of miRNA-based therapies, including the creation of miRNA mimics and inhibitors. Despite progress, there are still no approved RNA-based therapies for cancer treatment.2

 

 

Challenges of miRNA Therapeutics

miRNA therapeutics face numerous challenges including targeted delivery, specificity, stability, immune response, and toxicity. Overcoming these challenges is paramount for success. However, ongoing research continues to drive the evolution of novel therapeutic strategies with the potential to improve patient outcomes. To highlight the potential of miRNA therapies for lung cancer, we have focused on their application in target discovery in non-small cell lung cancer (NSCLC).

 

miRNAs as Targets for NSCLC

Using Causaly, targets for NSCLC can be identified. Causaly machine-reads the literature to extract a list of targets for NSCLC presented as a dendrogram view of results. This allows users to prioritize targets based on desired criteria, including study type and target class. Here we have used Causaly to identify miRNA targets in NSCLC:

  • All Targets: Almost 8000 targets associated with NSCLC were identified.
  • Genomic Studies: Approximately 1000 targets of NSCLC with genomics studies.
  • Target Class: Almost 100 targets classified as non-coding RNA molecules.
  • RNA Subclass: More than 50 targets were classified as microRNAs.
  • Relationship Type: 12 genes were shown to have downregulated relationship with NSCLC.
  • Linguistic Strength: MiR-144 was the microRNA with the highest evidence score.
MicroRNAs as Targets for Lung Cancer image 0
Figure 1. Dendrogram view of microRNAs with reported downregulated relationships with NSCLC.

MiR-144 as a miRNA Target

MiR-144 has gained attention as a potential therapeutic target in lung cancer due to its regulatory role in numerous biological processes, including cell proliferation, apoptosis and angiogenesis.3 The increased expression of miR-144 has shown to suppress NSCLCs both in vitro and in vivo.4 Developing drugs that activate miR-144 may therefore be promising avenue for the treatment of NSCLC.

 

Exploring further the mechanism by which miR144 can affect NSCLC, it was found that almost 20 pathways may be implicated, according to Causaly. Increased expression of miR-144 has shown to induce apoptosis in NSCLC.5 The overexpression miR-144 can also negatively regulate S-phase of cell cycle arrest and the migration of NSCLC cells.6

 

MiR-144 has also been implicated in drug resistance in NSCLC. Circular RNA, namely circRACGAP1, was shown to promote NSCLC growth by regulating miR-144-5p and CDKL1 signaling pathway.7 Knockdown of this circular RNA dramatically inhibited tumor growth and enhanced the sensitivity of NSCLC to Gefitinib in vitro and in vivo.7 In this study, miR-144-5p was shown to target CDKL1 to regulate cell cycle of NSCLC cells.7

 

Another study reported that the upregulation of X-Inactive Specific Transcript – a form of long ncRNA – is associated with cisplatin resistance in NSCLC via the downregulation of miR-144-3p.8 These findings underscore the therapeutic potential of miR-144 as a target to overcome drug resistance and improve treatment outcomes.

Conclusion

In conclusion, miRNA therapeutics hold significant potential in cancer treatment. Their ability to regulate gene expression and influence cellular behavior offers opportunities for targeted interventions. While challenges remain, ongoing research and development in miRNA-based therapies inspire optimism for innovative strategies in combating various types of cancer.

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References

  1. Peng, Y., Croce, C., Sig. Transduct. Target Ther., 2016;1(1):15004. Source
  2. Volpini, L., Monaco, F., Santarelli, L., et. al., Mol. Aspects Med.,2023;1(1):100005. Source
  3. Zhou, M., Wu, Y., Li, H., Zha, X., J. Cancer., 2020;11(22):6716-6726. Source
  4. Zhou, G., Cancer Biol. Med., 2019;16(4):700-713. Source
  5. Huang, Y., Ni, R., Wang, J., Liu, Y., Biomed. Pharmacother., 2019;109(1):1851-1859. Source
  6. Liang, Y., Zhang, D., Li, L., et. al., Stem Cell Res. Ther., 2020;11(1):87. Source
  7. Lu, M., Xiong, H., Xia, Z. K., et al., Cancer Gene Ther., 2021;28(1):197–211. Source
  8. Tian, L. J., Wu, Y. P., Wang, D., et. al., Med Sci Monit., 2019;25(1):8095-8104. Source

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