circPOLA2 promotes proliferation, invasion, migration, and epithelial-mesenchymal transition in breast cancer via the miR-1224-5p/HMGA2 axis.

OBJECTIVE

This study aimed to investigate the carcinogenic role of circPOLA2 in Breast Cancer (BC) and reveal its potential mechanism as a competitive endogenous RNA.

METHODS

Differentially expressed circRNAs, miRNAs, and mRNAs in BC tissues and cell lines were screened and analyzed by RT-qPCR. The interaction among circPOLA2, miR-1224-5p, and HMGA2 was tested using dual luciferase reporter assay and RNA pull-down assay. Cell proliferation was detected by MTT and colony formation assay, apoptosis was detected by flow cytometry, migration, and invasion was detected by Transwell assay, and EMT-related proteins were detected by Western blot.

RESULTS

circPOLA2 and HMGA2 levels were elevated in BC, while miR-1224-5p level was reduced. Knocking down circPOLA2 decreased the expression of HMGA2 by elevating miR-1224-5p expression. Knocking down circPOLA2 or HMGA2 or elevating miR-1224-5p reduced the proliferative, migratory, invasive, and anti-apoptotic capacities of BC cells.

CONCLUSION

Knockdown of circPOLA2 inhibits BC cell proliferation, migration, and invasion and delays BC tumor progression by regulating the miR-1224-5p/HMGA2 axis, providing a new strategy and target for therapeutic intervention in BC.