The Role of MicroRNA in Tumorigenesis: Article Summaries
In the article “Identification of Small Molecules That Suppress MicroRNA Function and Reverse Tumorigenesis,” Watashi, Yeung, Starost, Hosmane, and Jeang (2010) explain their cell-based model of microRNA (miRNA) related tumorigenesis that was used to observe the influence of two compounds that suppress miRNA pathways and potentially reverse tumorigenesis. While screening 530 compounds, the authors have found that polylysine (PLL) and trypaflavine (TPF) are relatively non-cytotoxic compounds that suppress miRNA activity. Watashi et al. (2010) have found that it could be possible to reverse tumorigenesis with those two compounds because they act as inhibitors for the miRNA-mediated silencing function. The exact mechanism of the PLL impact on Dicer activity and the mechanism that TPF uses to reduce the miRNAs interactions with the Argonaute 2 complex are not yet clearly explained. Although their research is promising, further research is required to examine if the PLL and TPF can reverse tumorigenesis with their influence on miRNAs.
In their literature review “MicroRNAs in Tumorigenesis: A Primer,” Zhang, Dhalberg, and Tham (2007) cover the basic biogenesis and functions of miRNAs and proceed to explain their roles in tumorigenesis. Researchers associate miRNA with several genomic alterations and indicate that miRNAs are not typical tumor suppressor genes because they activate their suppressing functions only when their levels are lower than critical, and the amount of resulting oncogenic gene products causes a tumor phenotype. While the authors confirm that miRNAs are key factors in oncogenesis, they also suggest that future research is required to confirm the role of miRNAs in tumorigenesis. The research on miRNA should mainly focus on actual situations to identify practical functions of each miRNA in tumorigenesis, and that data will allow clinicians to predict tumor behavior, potential metastasis development, and possible relapse scenarios. Besides diagnostics, it will be possible to alter miRNA pathways because they are identified as effective targets in treating cancer patients.
The article “Cancer Mechanisms: The Role of MicroRNAs in Cancer,” written by Espinosa and Slack (2006), addresses the recent discoveries that emphasized the role of miRNAs in cancer development. Although cancer mechanisms are not yet completely understood, research shows that miRNAs are responsible for regulating cell proliferation and apoptosis pathways that are altered in tumorigenesis, so that suggests their participation in tumorigenesis. Although some miRNAs have been identified as tumor suppressors, when they are exposed to genetic alterations, miRNAs can act as oncogenes and down-regulate tumor suppressors. Because research results on miRNAs often show contradictory findings, the authors suggest that clarifying their mechanisms further is the only way to apply them in cancer treatment. Although the application of anti-miRNA oligonucleotides (AMOs) is promising in rodent studies, AMOs do not differentiate between healthy and malignant cells. The therapeutic roles of miRNA in human patients can be expected only when the biogenesis and actions of miRNA is clearly explained.
Espinosa, C. E. S., & Slack F. J. (2006). Cancer mechanisms: The role of microRNAs in cancer. Yale Journal of Biology and Medicine, 79, 141-140.
Watashi, K., Yeung, M. L., Starost, M. F., Hosmane, R. S., & Jeang, K. (2010). Identification of small molecules that suppress microRNA function and reverse tumorigenesis. The Journal of Biological Chemistry, 285(32), 24707-24716.
Zhang, W., Dahlberg, J. E., & Tam, W. (2007). MicroRNAs in tumorigenesis: A primer. The American Journal of Pathology, 171(3), 728-738.
