Abstract P2-22-03: Effect of miR-660-5p in breast cancer progression

Abstract

Background: Breast cancer (BC) is the most diagnosed cancer in women worldwide. MicroRNAs (miRNAs) are involved in different processes of BC and their deregulation can cause them to act as oncogenes or tumor suppressors, participating in cancer progression or also as therapeutic target. Using The Cancer Genome Atlas (TCGA) database, we found that miR-660-5p is significantly overexpressed and associated with poor survival in patients with this pathology. Moreover, it is reported that miR-660-5p can induce BC progression through transcription factor CP2 (TFCP2) and the down regulation of tet-eleven translocation 2 (TET2). In this project, we propose to identify the role of miR-660-5p in proliferation, migration, invasion, angiogenesis, and possible targets involved in these processes in BC cell lines. Methods: Basal levels of miR-660-5p were determined in BC cells MDA-MB-231 and MCF-7, and in human epithelial breast cells MCF-10A by RT-qPCR. The effect of miR-660-5p was evaluated on proliferation, migration, and invasion processes using MDA-MB-231 and MCF-7 cells. HUVEC cells were used to assess angiogenesis. All cell lines were transfected with miR-660-5p inhibitor. Analysis of nine miRNA-target prediction databases was made to identify targets of miR-660-5p. We selected the target genes predicted by at least three of these programs, and their expression was evaluated by RT-qPCR in a customized 384-well plate. Results: We found that miR-660-5p is significantly upregulated in MDA-MB-231 and MCF-7, compared to MCF-10A cells. In addition, we observed a significant decrease in proliferation, migration, and invasion of BC cells transfected with miR-660-5p inhibitor, compared to non-treated cells and miRNA inhibitor negative control treated cells. Similarly, we observed a significant decrease in angiogenesis of HUVEC cells transfected with miR-660-5p inhibitor. Furthermore, of all the miR-660-5p targets identified by prediction databases 21 were selected, and of these, 7 were observed upregulated and 1 downregulated. Conclusions: The results show that miR-660-5p is upregulated and involved in proliferation, migration, invasion, and angiogenesis of BC, which may lead us to suggest that this miRNA act as an onco-miRNA. In addition, seven potential miR-660-5p target genes were identified, but further validation assays are needed to clarify their implication in this disease. Citation Format: Valeria Villarreal-García, José Roberto Estupiñan Jimenez, Ricardo Noriega, Recep Bayraktar, Diana Reséndez-Pérez, Cristina Rodríguez-Padilla, José Manuel Vázquez-Guillén, Gabriel Lopez-Berestein, Pablo E. Vivas-Mejía, Vianey Gonzalez-Villasana. Effect of miR-660-5p in breast cancer progression [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-22-03.