Abstract 1407: MicroRNA-18a targeting inhibits the tumor growth of cisplatin-resistant ovarian cancer

Abstract

Abstract Platinum-based therapy remains as the front-line treatment for ovarian cancer. However, despite initial response to treatment, most patients develop platinum resistance and eventually succumb to the malignancy. In an attempt to identify novel targets in cisplatin-resistant ovarian cancer, we studied the role of the microRNA-18a-5p (miR-18a) in cisplatin-resistant ovarian cancer. miR-18a is part of the vastly researched miR-17-92 cluster. Although most members of this cluster have been associated with pro-tumorigenic roles in several cancers, recent findings suggest that miR-18a plays a tumor-suppressive role in ovarian cancer. However, the specific role of miR-18a in platinum resistance has yet to be elucidated. In this study, Real-Time PCR analysis was performed to measure the levels of miR-18a in several ovarian cancer cell lines. We found miR-18a downregulation in cisplatin-resistant ovarian cancer cells relative to their sensitive counterparts. Therefore, we assessed the effect of miR-18a upregulation by oligonucleotide microRNA mimics (OMM) in tumor growth using a xenograft mouse model of cisplatin-resistant ovarian cancer. As ovarian tumors have been shown to overexpress the Folate Receptor α (FRα), we used nanoliposomes conjugated to folic acid as vehicles to deliver the OMMs. Following intraperitoneal injections of OMM-loaded liposomes (twice per week for three weeks), there was a significant decrease in tumor weight of miR-18a-OMM treated mice in comparison to the control-OMM group. Moreover, immunohistochemical analysis was performed on the mice tumor tissues to assess the levels of cell proliferation and angiogenesis markers (ki67 and CD31, respectively). Our study suggests that miR-18a halts cisplatin-resistant ovarian cancer tumor progression. This work was supported by the RCMI grant: U54 MD007600, UPR Comprehensive Cancer Center and NIGMS-RISE R25-GM061838. Citation Format: Blanca Iris Quiñones-Díaz, Jeyshka M. Reyes-González, Fatma Valiyeva, Pablo E. Vivas-Mejía. MicroRNA-18a targeting inhibits the tumor growth of cisplatin-resistant ovarian cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1407.