CircZFR serves as a prognostic marker to promote bladder cancer progression by regulating miR-377/ZEB2 signaling

Abstract

Circular RNAs (circRNAs) have been identified as crucial regulators of gene expression in human cancer biology. CircZFR is a novel identified circRNA and its effect in bladder cancer remains unclearly. In the present study, we aimed to investigate the role of circZFR in the progression of bladder cancer. First, we demonstrated that the expression of circZFR was higher in bladder cancer tissues and cells compared with adjacent non-tumor tissues and normal bladder epithelial cells. And higher circZFR levels were positively correlated with bladder cancer patients’ pathological T stage, grade, lymphatic metastasis, recurrence, progression-free survival (PFS) and overall survival (OS). Functionally, knockdown of circZFR could significantly prohibit cell growth, migration and invasion, arrest cell cycle as well as promote apoptosis of bladder cancer cells in vitro study. Mechanistically, we observed that circZFR could directly bind to miR-377 as sponge to promote ZEB2 expression in bladder cancer cells. In addition, rescue assays demonstrated that restoration of ZEB2 significantly impaired the suppressive effects of circZFR silencing on bladder cancer cells growth, migration and invasion. Taken together, our results illuminated that circZFR could be a prognostic biomarker in bladder cancer and exerted oncogenic roles through regulating miR-377/ZEB2 axis in bladder cancer, which indicated that circZFR could be a potential therapeutic target for bladder cancer patients treatment.

Circ_0072083 interference enhances growth-inhibiting effects of cisplatin in non-small-cell lung cancer cells via miR-545-3p/CBLL1 axis

“…CircRNAs could bind to miRNAs and function as miR-NAs sponges [20]. Accumulating articles have reported the downstream miRNAs of circ_0072083 in diverse cancers [25][26][27]. Herein, miR-545-3p was verified as a target of circ_0072083 in NSCLC cells.…”

<p>Circular RNAs and Bladder Cancer</p>

“…Further analysis showed that high levels of these circRNAs are closely related to the clinicopathological stage of BC, which describes the tumor status, including the tumor size, presence of local and distant metastasis, and tumor pathological grade, and affect the survival of BC patients. [27][28][29][30][31][32][33][34] Regarding tumor tissue classifications, the levels of circRNAs, including circ-BPTF, circTFRC, circZFR, circPTK2, and circASXL1, were found to be significantly higher in low-grade BC tissues than in high-grade BC tissues. 27,28,30,32,33 Regarding the pathological TNM stage, circRNAs, including circTFRC, circZFR, circPRMT5, circPTK2, circASXL1 and circCASC15, were positively correlated with the T stage when patients were stratified into Ta-1 and T2-4 subgroups.…”

“…[27][28][29][30][31][32][33][34] Regarding tumor tissue classifications, the levels of circRNAs, including circ-BPTF, circTFRC, circZFR, circPTK2, and circASXL1, were found to be significantly higher in low-grade BC tissues than in high-grade BC tissues. 27,28,30,32,33 Regarding the pathological TNM stage, circRNAs, including circTFRC, circZFR, circPRMT5, circPTK2, circASXL1 and circCASC15, were positively correlated with the T stage when patients were stratified into Ta-1 and T2-4 subgroups. 28,[30][31][32][33][34] Additionally, circTFRC, circZFR, circPRMT5, circPTK2 and circASXL1 were found to be closely related to lymph node status: BC patients with lymph node metastasis tended to have higher levels of these circRNAs.…”

“…27,28,30,32,33 Regarding the pathological TNM stage, circRNAs, including circTFRC, circZFR, circPRMT5, circPTK2, circASXL1 and circCASC15, were positively correlated with the T stage when patients were stratified into Ta-1 and T2-4 subgroups. 28,[30][31][32][33][34] Additionally, circTFRC, circZFR, circPRMT5, circPTK2 and circASXL1 were found to be closely related to lymph node status: BC patients with lymph node metastasis tended to have higher levels of these circRNAs. 28,[30][31][32][33] In addition, circASXL1 is associated with distant metastasis, and patients with BC with distant metastasis have higher levels of circASXL1.…”

“…28,[30][31][32][33][34] Additionally, circTFRC, circZFR, circPRMT5, circPTK2 and circASXL1 were found to be closely related to lymph node status: BC patients with lymph node metastasis tended to have higher levels of these circRNAs. 28,[30][31][32][33] In addition, circASXL1 is associated with distant metastasis, and patients with BC with distant metastasis have higher levels of circASXL1. 33 CircRNAs are related not only to pathological stage but also to clinical stage.…”