Abstract
BackgroundCircular 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.MethodsLevels 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.ResultsWe 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.ConclusionsCirc_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.
Highlights
Circular RNAs have been associated with bladder cancer (BC), but the specific underlying molecular mechanism of their association with BC development has not been fully explored
We designed convergent primers and divergent primers to amplify linear and circular RNA based on cDNA and genomic DNA from cell lines EJ and T24
By using real-time qPCR, we confirmed that circ_0008532 is resistant to RNase R, while MTGR1 mRNA is significantly reduced after RNase R treatment (Fig. 1 f)
Summary
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. Bladder cancer (BC) is one of the most common malignancies in the genitourinary system, with approximately 400,000 new cases diagnosed annually and over 165,000 deaths [1]. Treatment such as transurethral resection and intravesical chemotherapy may be successfully applied for non-muscle-invasive bladder cancer (NMIBC), the unfavorable prognosis and high rate of recurrence and metastasis of muscle-invasive bladder. Studies have reported that circRNAs regulate various biologic processes such as gene expression, transcription, cell. A recent study demonstrated that circ-TTBK2 decreases miR-217 expression and promotes glioma malignancy by regulating the miR217/HNF1β/Derlin-1 pathway [10]. Several circRNAs have been shown to act either as a tumor suppressor or an oncogene via different targets [11, 12]
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