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

Abstract

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.

Expression profiles, biological functions and clinical significance of circRNAs in bladder cancer

“…Proapoptotic effects of circ_Foxo3 have also been observed in breast carcinoma biopsies and in cancer cell lines [ 119 ]. Consistent with these findings, Li et al found by KEGG analysis that hsa_circ_0018069 may mediate the Foxo signalling pathway to exert anticancer effects [ 80 ] (Fig. 3 d).…”

“…For RT-PCR or Northern blotting, β-actin or GAPDH was used as a reference gene. Mean values, median expression levels, or concrete data are used as cut-off values [ 80 – 83 ]. No unified standards are available to determine thresholds for circRNA detection.…”

“…CircRNAs have been reported to be significantly associated with many clinicopathologic characteristics in BCa, including tumour size, grade, differentiation, and stage; lymph node metastasis (LNM); tumour numbers; distant metastasis (DM); invasion; and recurrence. Li et al observed that circ_0018069 is significantly downregulated in BCa tissues and in T24 and Biu-87 cells and that circ_0018069 levels are correlated with tumour grade, tumour stage, and muscular invasion depth in the context of BCa [ 80 ]. Circ_0137439 has also been reported to be significantly upregulated in urine samples from individuals with BCa.…”

MiR-362-5p, Which Is Regulated by Long Non-Coding RNA MBNL1-AS1, Promotes the Cell Proliferation and Tumor Growth of Bladder Cancer by Targeting QKI

“…A total of 24 pairs of bladder cancer tissues and matched adjacent tissues were collected from the patients who did not undergo radiotherapy or chemotherapy before surgery. The adjacent tissues were normal bladder tissues that collected at more than 3 cm away from the tumor tissues (Li et al, 2019a). All the tissues were immediately frozen in liquid nitrogen after surgical operation and stored at −80°C till use.…”

Circ_0006332 promotes growth and progression of bladder cancer by modulating MYBL2 expression via miR-143

“…The circRNA transcripts of PGM5 and KIAA1462 genes are significantly downregulated in bladder cancer [11]. Low expression of circ_00018069, a circRNA transcript from the KIAA1462 gene, is associated with the differentiation and muscular invasion of bladder cancer by modulating ErbB, Ras, FoxO and focal adhesion signaling pathways [12]. In the present study, we analyzed RNA-seq data and identified several differentially expressed circRNAs in bladder cancer tissue samples.…”