LncRNA MYO16-AS1 promotes proliferation, migration and invasion of ovarian cancer cells through regulation of MICAL2

OC has a 5-year survival rate of below 40% mainly due to diagnosis at late stages and recurrence associated to resistance to chemotherapy. LncRNAs affect several cellular functions with great physiological importance and perturbation of their expression is observed in several diseases including cancer, although the roles and functions of a majority of them remains poorly understood. We performed RNA-seq of 47 HGSOC samples; 28 with complete response to 1st line chemotherapy and 19 with partial response or stable disease. Among the genes differentially expressed, we found that the overexpression of MYO16-AS1, a poorly studied lncRNA, is associated with decreased OS in OC. Moreover, its downregulation affects proliferation, migration and invasion of OC SKOV3 cells. Through transcriptomic and proteomic analysis in SKOV3 cells we evidenced that MYO16-AS1 regulates genes involved in cellular proliferation, migration and invasion. Among those genes, we found that MICAL2 downregulation significantly inhibits SKOV3 cells proliferation, migration and invasion, suggesting that its regulation is the major determinant of MYO16-AS1 action in OC. Interestingly, MICAL2 inhibition did strongly reduce proliferation of several OC patient-derived tumor organoid models, irrespective of their response to chemotherapeutic treatment, highlighting MICAL2 as a potential target in OC.