Circ_0000190 inhibits the progression of triple negative breast cancer by regulating miR-301a/MEOX2 pathway.

Abstract

Circular RNA (circRNA) and microRNA (miRNA) play critical roles in regulating proliferation, apoptosis, and invasion in triple-negative breast cancer (TNBC) cells. To investigate their functional significance, we employed quantitative real-time PCR (qRT-PCR) to assess the differential expression of circ_0000190, miR-301a, and mesenchyme homeobox 2 (MEOX2) between TNBC cell lines and normal breast epithelial cells. Subsequently, we established overexpression and knockdown systems for these molecules to examine their effects on TNBC cell proliferation, apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT). Additionally, we evaluated the impact of circ_0000190 overexpression on tumor growth using a mouse xenograft model, measuring tumor volume and weight. Our findings revealed that circ_0000190 and MEOX2 expression were significantly downregulated (P<0.05) in TNBC cells compared to normal breast epithelial cells, whereas miR-301a was upregulated (P<0.05). Knockdown of circ_0000190 promoted TNBC cell proliferation, migration, invasion, and EMT, while suppressing apoptosis. Mechanistically, circ_0000190 functioned as a molecular sponge for miR-301a, and its overexpression significantly inhibited miR-301a expression (P<0.001). Notably, miR-301a mimics partially reversed the suppressive effects of circ_0000190 overexpression on proliferation, migration, invasion, and EMT, as well as its pro-apoptotic effects (P<0.001). Furthermore, we identified MEOX2 as a direct target of miR-301a. MEOX2 knockdown attenuated the inhibitory effects of miR-301a silencing on proliferation, migration, invasion, and EMT, while also counteracting its pro-apoptotic function. In vivo experiments demonstrated that circ_0000190 overexpression significantly reduced tumor volume and weight (P<0.001), concomitant with elevated MEOX2 mRNA and protein levels (P<0.001) and decreased miR-301a expression (P<0.001). In conclusion, our study elucidates that circ_0000190 suppresses TNBC progression by downregulating miR-301a and upregulating MEOX2, forming a competitive endogenous RNA (ceRNA) network of circRNA-miRNA-mRNA.