By Sharon Washio
Existing treatments for cancer have varying levels of success depending on the type, location, stage of cancer, and more. Such options include chemotherapy, radiation, drugs, or surgery, but those afflicted must often keep an eye out for relapse even when the cancer seems to momentarily go away. Though improved pharmaceuticals and enhanced prevention screenings have contributed to the decreasing death rate of cancer, the current available treatments are nonetheless associated with a plethora of unpleasant side effects. Additionally, with the steadily aging US population, the incidence of cancer is projected to increase in the future (NCI). As terminal cancer is caused by the unrestricted proliferation of cells, a possible treatment to turn to in the future is gene therapeutics, which deals with the cycles and expression of genes.
MicroRNAs (miRNAs) are non-coding RNA molecules that hold a significant role in gene regulation, especially that of tumors. miRNA therapy, or replacement therapeutics, is a recent field undergoing extensive research and clinical trials in hopes of becoming a viable treatment option for cancer in the future. Recently, an article by C. Liu, R. Liu, D. Zhang et al. published in Nature Communications on January 23 this year, detailed research by scientists from several different cancer institutes on the role of the microRNA-141 in prostate cancer. miR-141 was chosen because it is one of the miRNAs known to inhibit epithelial to mesenchymal transition (EMT), which is a process central to theprogression of cancer. Interestingly, previous reports on miR-141 failed to show conclusive results, in that miR-141 was sometimes reported to promote cancer.
The researchers used prostate cancer stem cells (CSCs), which are the cells that propagate the disease over long periods of time. By forcing expression of miR-141 in the CSC clusters using vectors, the researchers found that miR-141 negatively affected the cancer stem cells and tumor activity. The results have consistently supported miR-141’s metastatic suppression quality by showing that miR-141 repressed the activities of several molecules that aided cell proliferation, such as CD44+, Rho GTPases, and EZH2.
CD44+ is a cell surface marker molecule that allows enhanced cancer progression and is subsequently heavily associated with CSC populations. Researchers investigating the prostate cancer (PCa) cells found that miR-141 was consistently under-expressed in CSC clusters. Upon expressing miR-141 in the PCa cells, they found that it inhibited the metastatic aiding functions of the CD44+ cells such as cell overgrowth. Additionally, introducing miR-141 in sizable tumors showed that the microRNA reduced metastasis, and in doing so, the size of the primary tumor.
Like miR-34a, another microRNA currently in clinical trials for replacement therapeutics, immunofluorescence staining and invasion assays showed that miR-141 had a direct effect on CD44 cells—that is, wherever miR-141 was densely concentrated, CD44 would be under-expressed. In addition to this, miR-141 seemed to tamper with CSC growth and similar signaling processes necessary for tumor growth. Specifically, regarding PCa growth, miR-141 attacked Rho GTPases (proteins that regulate cellular activities) by interfering with their signaling. miR-141 also reduced EZH2 (enzymes that deal with histones) levels.
miR-141 therefore holds considerable potential in the novel realm of regenerative treatments. Since the process for introducing new medications can take years of clinical trials and testing, it is imperative that such nascent possibilities be extensively researched now.
A recurring and notable problem with miRNA investigations has been the conflicting results that the previous reports have produced. However, the conclusions reached through this publication have a steady consensus throughout and stands as one of the most extensive investigations done on the miR-141 molecule. More of the miR-200 family should be researched in different cancer settings to develop the replacement therapeutic field and thus make cancer treatments more effective and safe to administer.
Image source: (c) 2016 BioQuick News http://ichef-1.bbci.co.uk/news/660/media/images/82981000/jpg/_82981970_m8650341-prostate_cancer_cells,_sem-spl.jpg
Other relevant sources:
https://www.cancer.gov/about-cancer/understanding/statistics
http://www.cancerprogress.net/timeline/major-milestones-against-cancer
http://www.mirnarx.com/technology/mirna-replacement-therapy.html