CircWHSC1 regulates malignancy and glycolysis by the miR-212-5p/AKT3 pathway in triple-negative breast cancer

Background: Triple-negative breast Cancer (TNBC) is the most aggressive malignant tumor in breast Cancer (BC). Circular RNA circWHSC1 (circWHSC1) is connected with the progression of tumors. However, the role and regulatory mechanism of circWHSC1 in TNBC are unclear.

Methods: The expression of circWHSC1, MicroRNA (miR)-212-5p, and protein kinase B-3 (Akt3) mRNA in BC tissues and/or cells was examined by quantitative real-time polymerase chain reaction (qRT-PCR). The viability, colony formation, migration, invasion, and Apoptosis of TNBC cells were determined by cell counting kit-8 (CCK-8), colony formation, transwell, or flow cytometry assays. The levels of glucose consumption and lactate production were assessed with commercial kits. The levels of Hexokinase II (HK2) and Akt3 protein were detected by western blotting. The role of circWHSC1 in vivo was verified by tumor xenograft assay. The relationship between miR-212-5p and circWHSC1 or Akt3 was verified via dual-luciferase reporter and RNA pull-down assays.

Results: CircWHSC1 was upregulated in BC tissues and cells. Also, circWHSC1 could discriminate BC tissues and paracancerous normal tissues. TNBC patients with high circWHSC1 possessed a poor prognosis. CircWHSC1 silencing reduced TNBC cell growth in vivo and repressed proliferation, migration, invasion, glycolysis, and induced Apoptosis of TNBC cells in vitro. CircWHSC1 regulated Akt3 expression by sponging miR-212-5p. Silencing of miR-212-5p overturned circWHSC1 knockdown-mediated impacts on malignancy and glycolysis of TNBC cells. Akt3 overexpression reversed the inhibitory effect of miR-212-5p mimic on malignancy and glycolysis of TNBC cells.

Conclusions: CircWHSC1 accelerated malignancy and glycolysis of TNBC cells by the miR-212-5p/Akt3 axis. The research provided a potential prognostic biomarker and therapeutic target for TNBC.