miR-375 in Merkel Cell Carcinoma: An Intracellular Oncogene?
Posted: Wednesday, April 29, 2020
The miRNA known as miR-375 is highly abundant in Merkel cell polyomavirus–associated Merkel cell carcinoma, and free-circulating miR-375 serves as a surrogate marker for tumor burden in patients with advanced disease. Although miR-375 acts as either a tumor suppressor or oncogene in many other cancers, it does appear to do so in Merkel cell carcinoma, according to research findings published in Cancers.
“To explore the function of miRNAs [like miR-375], it is essential to achieve largely complete knockdown,” wrote Jürgen C. Becker, MD, PhD, of the University Hospital Essen, Germany, and colleagues. In fact, they did just that during the course of their study using antagomirs in classical Merkel cell carcinoma cell lines. (Also known as anti-miRs, antagomirs are oligonucleotides that prevent other molecules from binding to a desired site on an mRNA molecule.)
Apparently, miR-375 “has no relevant impact on the cell viability, metabolic activity, morphology, or oncogenic signaling pathways” it targets in Merkel cell carcinoma, the researchers concluded. Therefore, although miR-375 is unlikely to function as an intracellular oncogene, its function in this cancer remains unclear, warranting further research into “likely functions of miR-375 for the intercellular communication of Merkel cell carcinoma.”
Dr. Becker and co-investigators specified the methodology used for the knockdown. “Program D23 with 25nM miR-375 antagomirs was determined as the optimal protocol, [but] cells still showed a neuroendocrine growth pattern as loose spheroids or single cells, which was identical to the growth pattern in cells transfected with unspecific control antagomirs,” they noted. Further, “miR-375 target genes and related signaling pathways were determined, revealing [the] Hippo signaling and epithelial-to-mesenchymal transition–related genes likely to be regulated,” but the impact of miR-375 knockdown on those genes and pathways was “only marginal.”
Disclosure: The study authors’ disclosure information can be found at mdpi.com.
