Circ_0008532 promotes bladder cancer progression by regulation of the miR-155-5p/miR-330-5p/MTGR1 axis

Abstract

Background: Circular RNAs (circRNAs) have been associated with bladder cancer (BC), but the specific underlying molecular mechanism of their association with BC development has not been fully explored. Methods: Levels of Circ_0008532, MTGR1 and miR-155-5p/miR-330-5p in bladder cancer cell lines and tissues were determined with quantitative real-time PCR and western blotting assays. In vitro and in vivo assays were performed to investigate the function of circ_0008532 in tumorigenesis in bladder cancer cells. The relationships of Circ_ 0008532, MTGR1 and miR-155-5p/miR-330-5p were predicted using bioinformatic tools and verified by RNA-FISH, RIP and luciferase assays. The effects of circ_0008532 on the Notch signaling pathway were determined by GSEA analysis and western blotting assay. Results: We found that circ_0008532 is upregulated in BC cell lines and tissues. Moreover, overexpression of circ_ 0008532 promotes, and silencing of circ_0008532 inhibits the capacity for invasive in BC cells. In addition, circ_ 0008532 can directly interact with miR-155-5p and miR-330-5p as an miRNA sponge which mediates the expression of the miR-155-5p/miR-330-5p target gene MTGR1 and downstream Notch signaling. Conclusions: Circ_0008532 may act as an oncogene in BC through a novel circ_0008532/miR-155-5p, miR-330-5p /MTGR1/Notch pathway axis, which in turn may provide potential biomarkers and a therapeutic target for the management of bladder cancer.

CircRNAs: Emerging Bladder Cancer Biomarkers and Targets

“…Circ_0008532 was revealed as miR-155-5p and miR-330-5p sponge and could regulate the capacity for invasive in BC cells through MTGR1/Notch pathway. Circ_0008532 is up-regulated in BC cells and tissues, which acted as an oncogene in BC, which may provide potential biomarkers and a therapeutic target for the treatment of BC ( 50 ).…”

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

“…85 Similarly, hsa_circ_0008532 is overexpressed in BC and directly interacts with miR-155-5p and miR-330-5p to upregulate the MTGR1 expression and the downstream NOTCH signaling pathway. 86 NF-κB can induce regulatory signals in response to different stimuli and has been shown to play a key regulatory role in the physiological and pathological processes of various diseases, including cancer. 87 Compared with normal urethral epithelium, superficial BC tissue exhibits increased levels of NF-κB, while invasive BC tissue exhibits decreased levels; thus, the NF-κB-related pathway may function as a "double-edged sword" in tumor development.…”

Circ_0004913 sponges miR-1290 and regulates FOXC1 to inhibit the proliferation of hepatocellular carcinoma

“…Various circR-NAs exist in mammalian cells and regulate a broad range of biological processes through various mechanisms, including sponging of microRNAs (miRNAs) [10]. Cir-cRNA circ_0054537 could sponge miR-130a-3p to promote the progression of renal cell carcinoma through regulating cMet pathway, and circ_0008532 promotes bladder cancer progression by regulation of the miR-155-5p/miR-330-5p/MTGR1 axis [11,12]. However, the role of circ_0004913 in cancer is poorly understood.…”