Abstract
BackgroundBladder cancer is one of the most common cancers all over the world. CircZFR is a circular RNA and has been implicated in tumor generation and invasion. However, the exact role of circZFR in the development of bladder cancer (BCa) remains unknown. This study aimed to investigate the function of circZFR in BCa, and further to probe into the association between circ-ZFR, miR-545/miR-1270 and WNT5A.MethodsThe expression of circZFR in BCa was quantified by qRT-PCR and was positively correlated with the prognosis of BCa patients. Next, the stable knockdown of circZFR BCa cell lines was established and the resulting capacities of proliferation, migration and invasion were measured. The association of circZFR with miR-1270/miR-545 was predicted by circinteractome prediction, and was confirmed by luciferase assay as well as RNA pull down assay. Furthermore, miRNA inhibitors, WNT5A overexpression and Pearson correlation analysis were used to examine the relationship between circZFR, miR-1270/miR-545 and WNT5A.ResultsThe expression of CircZFR was up-regulated both in BCa tissues and in BCa cell lines, and was positively correlated with patient survival rates. Blocking of circZFR’s expression by RNA inhibitors suppressed the proliferation, migration and invasion of BCa cells both in vitro and in vivo. On the other hand, overexpression of target miRNA supported that circZFR directly interact with miR-545 and miR-1270. Moreover, we demonstrated that circZFR promotes the progression of BCa by upregulating WNT5A’s expression via sponging miR-545 and miR-1270.ConclusionsCircZFR promotes the proliferation, migration and invasion of BCa cells by upregulating WNT5A signaling pathway via sponging miR-545 and miR-1270. These results provide new insights into the molecular mechanism of circZFR in BCa progression, and more important, a novel target for BCa clinical treatment.
Highlights
Bladder cancer (BCa) is a notorious cancer worldwide, leading to more than 430,000 new diagnosed cases [1] and more than 165,000 deaths each year [2]
To investigate whether circZFR abundance was altered in BCa, four pairs of data were analyzed in GSE92675 dataset
We found that circZFR expression was increased in BCa tumor tissues compared with that in the adjacent normal tissues (Figure 1A)
Summary
Bladder cancer (BCa) is a notorious cancer worldwide, leading to more than 430,000 new diagnosed cases [1] and more than 165,000 deaths each year [2]. CircRNA-specific computation and high-throughput RNA sequencing are main tools for circRNA research [6]. Using these methods, the high expression of circZFR was found in thyroid cancer [7], rectal cancer [8], liver cancer [9, 10], lung cancer [11], kidney cancer [12], where circZFRs affect the occurrence and development of tumors through regulating the cell proliferation, invasion and migration. The exact role of circZFR in the development of bladder cancer (BCa) remains unknown. This study aimed to investigate the function of circZFR in BCa, and further to probe into the association between circ-ZFR, miR-545/miR-1270 and WNT5A
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