Circ_0006948 drives the malignant development of bladder cancer via activating the epithelial-mesenchymal transition.

Abstract

Purpose: To detect the expression characteristic of circ_0006948 in bladder cancer (BC), and to analyze its relationship with pathological parameters and prognosis in BC patients. In addition, molecular mechanisms of circ_0006948 on driving the malignant progression of BC by activating epithelial-mesenchymal transition (EMT) was explored.

Methods: Circ_0006948 levels in 72 BC and paracancerous tissues were detected, and their relationship with pathological parameters and prognosis in BC patients was analyzed by chi-square test. After establishing circ_0006948 knockdown model in 253j and T24 cells, phenotype changes were assessed by cell counting kit-8 (CCK-8), transwell and wound healing assay. Regulatory effects of circ_0006948 on EMT-associated gene expressions in BC cells were determined by Western blot. Finally, the interaction between circ_0006948 and N-cadherin was evaluated by rescue experiments.

Results: Circ_0006948 was upregulated in BC tissues and cell lines. High level of circ_0006948 indicated advanced tumor stage, high rates of lymph node metastasis and distant metastasis, and poor prognosis in BC. Knockdown of circ_0006948 reduced proliferative and metastatic abilities in BC cells. The key protein in the EMT signaling E-cadherin was upregulated by knockdown of circ_0006948 in BC cells, while N-cadherin, Vimentin, β-catenin and MMP-9 were downregulated. The interaction between circ_0006948 and N-cadherin was identified, and they were co-responsible for the malignant development of BC.

Conclusions: Circ_0006948 is upregulated in BC samples, and it is closely linked to tumor stage, metastasis and prognosis in BC patients. It drives proliferative and metastatic abilities in BC cells by activating EMT.