Dataset Information

Comprehensive circular RNA profiling reveals the regulatory role of circ_100242/miR-145 pathway in bladder cancer.

ABSTRACT: Bladder cancer is a common genitourinary carcinoma with high morbidity and mortality rates. Circular RNAs (circRNAs), which are a type of single-stranded RNAs, have been characterized as stable, conserved and tissue-specific molecules in mammalian cells. The present study explored the circRNA expression profile in four bladder cancer tissues and matched normal samples by using microarray analysis. Furthermore, bioinformatics analyses were performed to investigate the potential function of dysregulated circRNAs in bladder cancer. The results demonstrated that 89 circRNAs were downregulated and 210 circRNAs were upregulated in bladder cancer tissues. The results from RT-qPCR demonstrated that hsa_circ_100241, hsa_circ_100242 and hsa_circ_101303 were markedly upregulated whereas hsa_circ_104510 was significantly downregulated in bladder cancer tissues compared with normal tissue. Following circRNA/microRNA (miRNA) interaction network generation via Cytoscape, it was demonstrated that hsa_circ_100242 contained a miRNA response element for miR-145-5p, which is a tumor suppressor in bladder carcinoma. In addition, results from the Kyoto Encyclopedia of Genes and Genomes analysis showed that the MAPK signaling pathway was the most significant pathway of the differentially expressed circRNAs in bladder cancer tissues. In conclusion, the present study demonstrated that circRNAs were dysregulated in bladder cancer tissues compared with matched normal samples. Pathway analysis was also performed to predict the binding of miRNAs to the dysregulated circRNAs. The results revealed that hsa_circ_100242 may be involved in bladder cancer initiation and progression by sponging miR-145. These findings may provide further insights into the functional and therapeutic roles of circRNAs in bladder cancer.

SUBMITTER: Zhu Z

PROVIDER: S-EPMC7068268 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Comprehensive circular RNA profiling reveals the regulatory role of circ_100242/miR-145 pathway in bladder cancer.

Zhu Zhaowei Z Chang Fujiang F Liu Junxiao J Wang Jiange J Zhang Xuepei X

Oncology letters 20200210 4

Bladder cancer is a common genitourinary carcinoma with high morbidity and mortality rates. Circular RNAs (circRNAs), which are a type of single-stranded RNAs, have been characterized as stable, conserved and tissue-specific molecules in mammalian cells. The present study explored the circRNA expression profile in four bladder cancer tissues and matched normal samples by using microarray analysis. Furthermore, bioinformatics analyses were performed to investigate the potential function of dysreg ...[more]

PMID: 32218853

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Project description:Bladder cancer (BC) is one of the most common malignant tumors in males globally. Its progression imposes a heavy burden on patients; however, the expression profile of circular (circ)RNAs in BC progression remains unclear. This study explored changes in circRNA expression during BC progression by sequencing different grade BC samples and normal controls to reveal the circRNA expression profiles of different BC grades. Gene Ontology (GO) and Kyoto Encyclopedia of Gens and Genomes (KEGG) pathway analyses, and protein‑protein interaction network construction were used to predict pathways that the differentially expressed circRNAs may participate in. circRNA expression levels were detected using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and dual‑luciferase reporter assays were used to investigate the interactions between circRNA and microRNA (miR). Cell Counting Kit‑8 and Transwell assays were also performed to detect cell proliferation, migration, and invasion. In total, 244 circRNAs were found to be differentially expressed in high‑grade BC compared to low‑grade BC, whilst 316 dysregulated circRNAs were detected in high‑grade BC compared with normal urothelium. Furthermore, 42 circRNAs overlapped between the two groups, seven of which were randomly selected and detected by RT‑qPCR to validate the sequencing results. GO analysis and KEGG pathway analyses revealed that the differentially expressed circRNAs may participate in BC via 'GTPase activity regulation', 'cell junction', and 'focal adhesion' pathways. Of note, we proposed that a novel circRNA in BC progression, hsa_circ_0137606, could suppress BC proliferation and metastasis by sponging miR‑1231. Through bioinformatics analysis, we predicted that PH domain and leucine rich repeat protein phosphatase 2 could be a target of the hsa_circ_0137606/miR‑1231 axis in BC progression. Using high‑throughput sequencing, this study revealed the circRNA expression profiles of different grades of BC and proposed that the novel circRNA, hsa_circ_0137606, suppresses BC proliferation and metastasis by sponging miR‑1231. Our findings may provide novel insight into potential therapeutic targets for treating BC.

Project description:Objectives: Circular RNAs (circRNAs) are involved in carcinogenesis, though their expression profile in renal cell carcinoma (RCC) is uncharacterized. The tumor suppressor gene miR-145-5p is expressed in RCC tissues, but its relationship with circRNAs is unknown. Thus, we aimed to identify differentially expressed circRNAs in RCC tissues and to explore the interaction between these circRNAs and miR-145 in the development of RCC. Methods: We performed high-throughput sequencing and bioinformatics analyses to examine the expression pattern of circRNAs in RCC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to functionally annotate differentially expressed circRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was used for sequence verification. Small interfering RNAs were employed to investigate the function and mechanism of circRNAs in RCC. The relationship between miR-145-5p and circRNAs was confirmed using luciferase, RNA immunoprecipitation (RIP), and biotin-coupled probe RNA pull-down assays. Results: Fifty-three circRNAs were significantly and differentially expressed in RCC compared to normal control tissue. Bioinformatic analyses indicated that two significantly upregulated circRNAs, circ-AFF2 and circ-ASAP1, had sequences corresponding to miR-145 response elements. Consistently, the luciferase reporter, RIP, and biotin-coupled probe RNA pull-down assays showed that circ-AFF2 and circ-ASAP1 may repress miR-145 by acting as sponges. circ-AFF2 and circ-ASAP1 were highly expressed in RCC patient-derived tumor samples; their overexpression correlated with poor prognosis and low miR-145 levels. Knockdown of circ-AFF2 or circ-ASAP1 in RCC cell lines inhibited proliferation, underscoring their oncogenic function. A circRNA-miRNA network was constructed for RCC using the differentially expressed circRNAs and projected miRNAs. Candidate genes were verified by RT-qPCR and western blot, indicating that circ-AFF2 and circ-ASAP1 may be connected to RCC proliferation and metastasis. Conclusion: circ-AFF2 and circ-ASAP1 were upregulated in RCC and likely promote tumor progression by sponging miR-145. Therefore, both circRNAs should be investigated further as potential diagnostic and therapeutic targets for RCC.

Project description:Recent evidence has demonstrated that circular RNAs (circRNAs) played crucial roles in fine-tuning the levels of gene expression by sequestering the corresponding microRNA (miRNAs). Their interaction with disease-associated miRNAs indicates that circRNAs are important for the development of disease, and miR-145 has been previously shown to have antitumor effect in prostate cancer. In the current study, we successfully established the miR-145-overexpressed prostate cancer LNCaP cells (LNCaP-miR-145) using lentiviral vectors. LNCaP cells expressing the empty vector (LNCaP-NC) were used as the negative control. The circRNA expression in LNCaP-miR-145 cells was detected by microarray analysis, and the miRNA targets of circRNAs were predicted using the bioinformatics software TargetScan and miRanda. Quantitative reverse transcription polymerase chain reaction was used to detect the expression levels of circRNAs in the prostate cancer tissue, nonmalignant tissue, LNCaP-miR-145 cells, and LNCaP-NC cells. The interaction of miRNA and circRNA was further confirmed by the dual-luciferase reporter assay. A total of 267 and 149 circRNAs were significantly up- and downregulated in LNCaP-miR-145 cells, respectively. hsa_circRNA_101981, hsa_circRNA_101996 and hsa_circRNA_09142 were the 3 circRNAs that interacted with hsa-miR-145-5p; hsa_circRNA_008068 and hsa_circRNA_406557 were the 2 circRNAs that interacted with hsa-miR-145-3p. Most of the circRNAs corresponded to the protein-coding exons. The expression levels of hsa_circRNA_101981, hsa_circRNA_00806, and hsa_circRNA_406557 were upregulated in the LNCaP-miR-145 cells, but downregulated in the prostate cancer tissue. In contrast, the expression levels of hsa_circRNA_101996 and hsa_circRNA_091420 were downregulated in the LNCaP-miR-145 cells, but upregulated in the prostate cancer tissue. Moreover, miR-145-5P might regulate the expression of hsa_circRNA_101981, hsa_circRNA_101996, and hsa_circRNA_09142, while miR-145-3P might regulate the expression of hsa_circRNA_008068 and hsa_circRNA_406557. Overexpression of miR-145 promoted the expression of hsa_circRNA_101981, hsa_circRNA_008068, and hsa_circRNA_406557 but suppressed the expressions of hsa_circRNA_101996 and hsa_circRNA_091420 in LNCaP cells. The results from the current study should give us a clue to clarify the tumor suppressive effect of miR-145.

Dataset Information

Comprehensive circular RNA profiling reveals the regulatory role of circ_100242/miR-145 pathway in bladder cancer.

Publications

Comprehensive circular RNA profiling reveals the regulatory role of circ_100242/miR-145 pathway in bladder cancer.

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