The tumor suppressor 5A2, a synthetic miR-7-5p mimic, targets oncogenic and metabolic pathways, as revealed by transcriptome-wide analysis

The tumor suppressor 5A2, a synthetic miR-7-5p mimic, targets oncogenic and metabolic pathways, as revealed by transcriptome-wide analysis

Blog Article

As cancer is a multifactorial disease, the multimodal action of microRNAs makes them an attractive tool for novel therapeutic approaches.The tumor suppressive miR-7-5p has been shown to Computer Fan Power Adaptor act on many aspects of oncogenesis, including cell proliferation, migration and angiogenesis, by targeting a spectrum of key genes.We developed a synthetic chemically modified miR-7-5p mimic, 5A2, and performed a comprehensive functional characterization in a panel of human cancer cell lines.5A2 reduced cell proliferation in most cell lines by inducing cell cycle arrest.

To enable systemic delivery of 5A2 to tumors, it was formulated in a novel lipid nanoparticle (INT-5A2) and we demonstrated the anti-tumor activity of INT-5A2 in an experimental human liver Kitchen Knives tumor-bearing mouse model.Next, RNA-sequencing was used to gain more insight into the molecular mechanism of action of 5A2 and demonstrated a broad repression of target mRNAs.Interestingly, Ingenuity Pathway Analysis revealed a new role for 5A2 in metabolic pathways.Validation experiments in vitro showed that 5A2 reduced the expression of key glycolysis and glutaminolysis enzymes, leading to a decrease in glycolysis, lactate secretion and intracellular glutamate availability.

Taken together, these data strongly suggest that miR-7-5p/5A2 is a potent tumor suppressor that targets various key cellular pathways across cancer types.Therefore, 5A2 may represent a promising novel treatment strategy in oncology.