GSE129076
miR-450a acts as a tumor suppressor in ovarian cancer by readjusting energy metabolism
Dysregulation of miRNA expression is associated with multiple diseases, including cancers where they can have oncogenic or tumor suppressive function. Here we investigated the potential tumor suppressive function of miR-450a, one of the most significantly downregulated miRNAs in ovarian cancer. RNAseq analysis revealed multipe genes involved in the epithelial-to-mesenchymal transition (EMT) were suppressed by miR-450a overexpression ovarian cancer cell line A2780. Consistently, miR-450a overexpression reduced tumor migration, invasion and increased anoikis in A2780 and SKOV-3 cell lines and reduced tumor growth in ovarian xenographic model. Combining AGO-PAR-CLIP and RNAseq analysis, we identified a panel of potential miR-450a targets of which many, including TIMMDC1, MT-ND2, ACO2 and ATP5B, regulate energetic metabolism. miR-450a expression indeed decreased mitochondrial membrane potential but increased glucose uptake and viability after glutamine withdrawal, characteristics of less invasive ovarian cancer cell lines, which are also less dependent on glutamine. In summary, we propose in this work that miR-450a acts as a tumor suppressor in ovarian cancer cells by modulating targets associated with glutaminolysis, which would lead to a decrease in the production of lipids, amino acids and nucleic acids, and also inhibition of signaling pathways associated with EMT Overall design: RNA-Seq from 3 different biological samples from SKOV3 and A2780 cell lines after miR-450a overexpression; small RNA-Seq from 3 different biological from A2780 cell line after miR-450a or miR-450b overexpression; AGO 4SU-PAR-CLIP from 2 to 4 biological samples from A2780 cells lines after miR-450a overexpression.