Cobomarsen, an Oligonucleotide Inhibitor of miR-155, Coordinately Regulates Multiple Survival Pathways to Reduce Cellular Proliferation and Survival in Cutaneous T-Cell Lymphoma

miR-155 is a microRNA associated with poor prognosis in lymphoma and leukemia and has been implicated in the progression of Mycosis Fungoides (MF), the most common form of cutaneous T-cell lymphoma (CTCL). In this study, we developed and tested Cobomarsen (MRG-106), a locked nucleic acid-modified oligonucleotide inhibitor of miR-155. In MF cell lines in vitro, inhibition of miR-155 with Cobomarsen de-repressed direct miR-155 targets, decreased expression of multiple gene pathways associated with cell survival, reduced survival signaling, decreased cell proliferation, and activated apoptosis. We identified a set of genes that are significantly regulated by Cobomarsen, which includes direct and downstream targets of miR-155. CTCL cell lines were cultured with Cobomarsen (MRG-106) for 4 days (to identify direct targets) or 8 days (to identify downstream targets).