Background: Triple negative breast cancer (TNBC), a special subtype of breast cancer, is characterized by high recurrence, mortality and few treatments. To date, the key factors contributing to TNBC progression have not been fully identified. In the current study, we found a TNBC-related circular RNA (circRNA), circ-PGAP3, and explored its biological function, clinical significance and potential mechanism of action.
Materials and Methods: The functional assay was carried out using CCK-8, colony formation and Transwell invasion assays. RIP, RNA pull-down and luciferase reporter assays were used to test the correlation between circ-PGAP3, miR-330-3p and Myc. The animal model was employed to verify the function of circ-PGAP3 in vivo.
Results: Circ-PGAP3 expression was significantly increased in TNBC tissues. High circ-PGAP3 was closely associated with large tumor size, lymph node metastasis, later TNM stage and dismal outcome. Through performing a series of in vitro and in vivo experiments, we found that circ-PGAP3 promoted TNBC cell growth and metastasis via sponging and inhibiting miR-330-3p, resulting in the upregulation of proto-oncogene Myc. Importantly, circ-PGAP3 expression was positively correlated with the Myc protein level but negatively correlated with miR-330-3p expression in TNBC tissues. Moreover, silencing of miR-330-3p or overexpression of Myc could effectively rescue the weakened malignant phenotype induced by circ-PGAP3 knockdown.
Conclusion: Our results unveil the important driving role of circ-PGAP3 in TNBC development and progression, which provides a candidate therapeutic target for TNBC patients.
Keywords: triple negative breast cancer, circular RNA, miRNA, Myc