Dysregulation of miRNA expression is associated with multiple diseases, including cancers, in which small RNAs can have either oncogenic or tumor suppressive functions. The RNA Molecular Biology Group, in collaboration with researchers from the University of Sāo Paulo, investigated the potential tumor suppressive function of miR-450a, one of the most significantly downregulated miRNAs in ovarian cancer. Overexpression of miR-450a in ovarian cancer cell lines suppressed multiple genes involved in the epithelial-to-mesenchymal transition (EMT). Overexpression of miR-450a reduced tumor migration and invasion, increased cell death, and reduced tumor growth in an ovarian tumor xenographic model. Researchers identified a panel of potential miR-450a target genes of which many regulate energetic metabolism. Following glutamine withdrawal, miR-450a overexpression decreased mitochondrial membrane potential but increased glucose uptake and viability, characteristics of less invasive ovarian cancer cell lines. In summary, the authors propose that miR-450a acts as a tumor suppressor in ovarian cancer cells by modulating targets associated with glutaminolysis, which leads to decreased production of lipids, amino acids, and nucleic acids as well as inhibition of signaling pathways associated with EMT.
Read the abstract (access to full article requires subscription or payment):
miR-450a acts as a tumor suppressor in ovarian cancer by regulating energy metabolism