Abstract 2103: miR-140 and miR-192 are potential tumor suppressors through inhibiting cellular proliferation and restoring cell cycle control in breast cancer cell lines

Abstract

Abstract Abstract MicroRNAs (miRNAs) are a class of small non-coding RNAs in regulating expressions of multiple mRNA targets mostly by binding at the 3’-UTRs to inhibit mRNA translation or facilitate mRNA cleavage. MiRNAs are involved in the control of many fundamental cellular and physiological processes and mounting evidence indicates that miRNAs play important roles in human cancers acting either as oncogenes or tumor suppressor genes through their global impact on multiple genes and pathways. Previous studies from our group have discovered two important miRNAs, miR-140 and miR-192, in suppression of cellular proliferation and triggering cell cycle arrest in both colon cancer and osteosarcoma cell lines. In this study, we further elucidate the molecular and cellular impact of these two miRNAs in breast cancer. miR-140 or miR-192 were over-expressed by transient transfection in a panel of breast cancer cell lines such as MCF-7 and MDA-MB-231. The proliferation of MCF-7 cells transfected with miR-140 or miR-192 was dramatically decreased at 100 nM while the control miRNA has no effect. Inhibition of proliferation by miR-140 or miR-192 was also observed in MDA-MB-231 cells but less potent than MCF-7 cells at the equal concentration. MCF-7 cells transfected with miR-140 or miR-192 were arrested at G2/M phase of the cell cycle. The cell cycle check point control genes p53 and p21 were induced by over-expressing miR-140 or miR-192. The endogenous miR-140 or miR-192 expression was induced in MCF-7 cells treated with methotraxate (MTX) accompanied with increased expression of p53. Blocking endogenous miR-140 or miR-192 by locked nucleic acid (LNA) modified anti-miRNA increased cellular proliferation rate in MCF-7 cells. In conclusion, miR-140 and miR-192 may have therapeutic potential in breast cancer. Keywords: microRNA, breast cancer, miR-140, miR-192 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2103.