Molecular tumor board (MTB): Development of clinical pathways for precision medicine. Experiences of center for breast cancer at national cancer center, Korea

Abstract

Background: The aim of the current study was to investigate the role of Circular RNA(circRNA) circASS1 in breast cancer(BC) cells, and this may be a novel therapy and a potential diagnostic biomarker or targeted treatment of BC. Methods: We analyzed the expression profile of human circRNAs in two BC cell lines: MCF-7, MDA-MB-231 by the circRNAs microarray, and we found the dysregulated circRNA: circASS1. Then the expression of circASS1 in breast cancer cells were identified. Next, measure of the abilities of invasion and migration were carried out by overexpressing circASS1 or silencing circASS1 in MDA-MB-231 and MCF-7, respectively. Luciferase Assay System were also carried out to detect harbored miRNA. Then, measure of the abilities of invasion and migration were carried out by overexpressing miR-4443 mimics. At last, the expression of circASS1's parental gene, ASS1 in gain-of-function and loss-of-function experiments were also quantitative analyzed. Results: Compared with MCF-7, the expression level of circASS1 in MDA-MB-231 is down-regulated. What is more, the results show overexpression of circASS1 could suppress invasion and migration in MDA-MB-231. On the contrary, silence of circASS1 could promote invasion and migration in MCF-7. miR-4443 could be captured by circASS1 according to Luciferase Assay System results, which could promote the ability of invasion and migration in MCF-7. Last, the expression of ASS1 is up-regulated in loss-of-function experiments, while down-regulated in gain-of-function experiments. Western blotting showed ASS1 up-regulated in loss-of-function experiments. Conclusions: CircASS1 suppresses invasion and migration capacity of BC cells by increasing expression of ASS1 and circASS1 could harbor miR-4443, suggesting that circASS1 could be a potential target in BC treatment and a prospective prognostic biological marker in BC.