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Abnormal expression of noncoding RNA molecules such as circRNA plays an important role in the development of malignant tumors. circRNAs are stable in structure and can be useful as ideal tumor markers. Advanced bladder cancer has poor treatment options and prognosis. Thus, we examined circRNAs to further understand the pathogenesis and development of bladder cancer and to identify molecular markers for the early diagnosis of bladder carcinoma. We found that hsa_circ_0018069 was differentially expressed in our RNA sequencing data. We used qRT-PCR to detect its expression in T24 and Biu-87 cell lines and in 41 paired samples of bladder cancer and adjacent normal tissue and analyzed the correlation between expression of hsa_circ_0018069 and the clinical characteristics of patients with bladder cancer. We then performed a bioinformatics analysis to reveal the mechanism of hsa_circ_0018069 in tumorigenesis of bladder cancer. The expression of hsa_circ_0018069 was significantly reduced in T24 and Biu-87 cells and was also significantly downregulated in bladder cancer tissues. Decreased expression of hsa_circ_0018069 was related to the grade stage (P=0.024), T stage (P=0.027), and muscular invasion depth (P=0.022) of bladder cancer. Bioinformatics analysis showed that hsa_circ_0018069 was coexpressed with protein-coding mRNAs that participate in cytoskeletal protein binding and cell-substrate junction assembly and play an anticancer role through focal adhesion and calcium signaling pathways. ceRNA analysis showed that hsa_circ_0018069 functions in ErbB, Ras, FoxO, and the focal adhesion signaling pathway by harboring miR-23c, miR-34a-5p, miR-181b-5p, miR-454-3p, and miR-3666. hsa_circ_0018069 may thus play an important role in the occurrence and progression of bladder cancer and serve as a valuable biomarker for the early diagnosis of this disease.

Low Expression of hsa_circ_0018069 in Human Bladder Cancer and Its Clinical Significance