Exosomal microRNAs (miRNAs) are suggested to reflect molecular changes occurring in their cells of origin and are potential indicators in the early detection of cancers. This study aimed to determine whether certain exosomal miRNAs from tumor tissue can be used as noninvasive biomarkers for clear cell renal cell carcinoma (ccRCC). Based on ccRCC miRNA expression profiles and the literature, we selected six miRNAs (miR‐210, miR‐224, miR‐452, miR‐155, miR‐21, and miR‐34a) and analyzed their expression in tissues, sera, and serum exosomes through quantitative real‐time polymerase chain reaction in hypoxia‐induced (with CoCl2) renal cell lines. miR‐210, miR‐224, miR‐452, miR‐155, and miR‐21 were upregulated in tumor tissues compared with normal tissues. Serum miR‐210 and miR‐155 levels were higher in patients with ccRCC than in healthy controls (HCs). Furthermore, only exosomal miR‐210 was significantly upregulated in patients with ccRCC than in HCs. Moreover, receiver operating characteristic (ROC) curve analysis revealed an area under the ROC curve of 0.8779 (95% confidence interval, 0.7987‐0.9571) and a sensitivity and specificity of 82.5% and 80.0%, respectively. Moreover, exosomal miR‐210 was upregulated at an advanced stage, and Fuhrman grade and metastasis decreased significantly one month after surgery. Acute hypoxia exposure activates miR‐210 and release of exosomes with upregulated miR‐210 in both normal and tumor RCC cell lines and interferes with vacuole membrane protein 1 mRNA expression, especially in the metastatic ccRCC cell line. In conclusion, Serum exosomal miR‐210 originating from tumor tissue has potential as a novel noninvasive biomarker for the detection and prognosis of ccRCC.
BackgroundThis study aimed to investigate the effect of over-expressing circular RNA CEP128 (circCEP128) on cell functions and explore the molecular mechanism of which in bladder carcinoma.MethodsThe differentially expressed circRNAs and mRNAs in bladder carcinoma cells and cells in adjacent tissues were screened out using microarray analysis. Expression levels of circRNAs and mRNAs in tissues and cells were determined by qRT-PCR. Expression of SOX11 was detected by western blot. Luciferase reporter assay and RNA pull-down assay were used to investigate the interactions between the specific circRNA, miRNA and mRNA. Cell cycle and apoptosis were measured using flow cytometry after transfection. MTT assay was also performed to detect the cell proliferation.ResultsIn present study, circCEP128 and SOX11 were observed significantly up-regulated in bladder cancer tissues, while the expression of miR-145-5p was decreased in cancer samples compared to normal samples. Cytoscape was used to visualize circCEP128-miRNA-target gene interactions based on the TargetScan and circular RNA interactome, which revealed that circCEP128 served as a sponge of miR-145-5p and indirectly regulated SOX11. Knockdown of circCEP128 induced the inhibition of cell proliferation and the increased bladder cancer cell apoptosis rate.ConclusionsCircCEP128 functions as a ceRNA for miR-145-5p, which could up regulates SOX11 and further promotes cell proliferation and inhibits cell apoptosis of bladder cancer.
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