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

Zhu,Zhaowei; Zhu,Zhaowei; Chang,Fujiang; Chang,Fujiang; Liu,Junxiao; Liu,Junxiao; Wang,Jiange; Wang,Jiange; Zhang,Xuepei; Zhang,Xuepei

doi:10.3892/ol.2020.11380

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

Authors:
- Zhaowei Zhu
- Fujiang Chang
- Junxiao Liu
- Jiange Wang
- Xuepei Zhang
View Affiliations

Affiliations: Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: February 10, 2020 https://doi.org/10.3892/ol.2020.11380
Pages: 2971-2978

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

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.

View Figures

View References

1	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
2	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2018. CA Cancer J Clin. 68:7–30. 2018. View Article : Google Scholar : PubMed/NCBI
3	Pasquinelli AE: MicroRNAs and their targets: Recognition, regulation and an emerging reciprocal relationship. Nat Rev Genet. 13:271–282. 2012. View Article : Google Scholar : PubMed/NCBI
4	Rupaimoole R and Slack FJ: MicroRNA therapeutics: Towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov. 16:203–222. 2017. View Article : Google Scholar : PubMed/NCBI
5	Li Y and Wang X: Role of long noncoding RNAs in malignant disease (Review). Mol Med Rep. 13:1463–1469. 2016. View Article : Google Scholar : PubMed/NCBI
6	Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, Maier L, Mackowiak SD, Gregersen LH, Munschauer M, et al: Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 495:333–338. 2013. View Article : Google Scholar : PubMed/NCBI
7	Qu S, Yang X, Li X, Wang J, Gao Y, Shang R, Sun W, Dou K and Li H: Circular RNA: A new star of noncoding RNAs. Cancer Lett. 365:141–148. 2015. View Article : Google Scholar : PubMed/NCBI
8	Li Y, Zheng Q, Bao C, Li S, Guo W, Zhao J, Chen D, Gu J, He X and Huang S: Circular RNA is enriched and stable in exosomes: A promising biomarker for cancer diagnosis. Cell Res. 25:981–984. 2015. View Article : Google Scholar : PubMed/NCBI
9	Guo S, Xu X, Ouyang Y, Wang Y, Yang J, Yin L, Ge J and Wang H: Microarray expression profile analysis of circular RNAs in pancreatic cancer. Mol Med Rep. 17:7661–7671. 2018.PubMed/NCBI
10	Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK and Kjems J: Natural RNA circles function as efficient microRNA sponges. Nature. 495:384–388. 2013. View Article : Google Scholar : PubMed/NCBI
11	Liu BH, Zhang BB, Liu XQ, Zheng S, Dong KR and Dong R: Expression profiling identifies circular RNA signature in hepatoblastoma. Cell Physiol Biochem. 45:706–719. 2018. View Article : Google Scholar : PubMed/NCBI
12	Qian Y, Lu Y, Rui C, Qian Y, Cai M and Jia R: Potential significance of circular RNA in human placental tissue for patients with preeclampsia. Cell Physiol Biochem. 39:1380–1390. 2016. View Article : Google Scholar : PubMed/NCBI
13	Yang X, Yuan W, Tao J, Li P, Yang C, Deng X, Zhang X, Tang J, Han J, Wang J, et al: Identification of circular RNA signature in bladder cancer. J Cancer. 8:3456–3463. 2017. View Article : Google Scholar : PubMed/NCBI
14	Li M, Liu Y, Zhang X, Liu J and Wang P: Transcriptomic analysis of high-throughput sequencing about circRNA, lncRNA and mRNA in bladder cancer. Gene. 677:189–197. 2018. View Article : Google Scholar : PubMed/NCBI
15	Li P, Yang X, Yuan W, Yang C, Zhang X, Han J, Wang J, Deng X, Yang H, Li P, et al: CircRNA-cdr1as exerts anti-oncogenic functions in bladder cancer by sponging MicroRNA-135a. Cell Physiol Biochem. 46:1606–1616. 2018. View Article : Google Scholar : PubMed/NCBI
16	Zhong Z, Huang M, Lv M, He Y, Duan C, Zhang L and Chen J: Circular RNA MYLK as a competing endogenous RNA promotes bladder cancer progression through modulating VEGFA/VEGFR2 signaling pathway. Cancer Lett. 403:305–317. 2017. View Article : Google Scholar : PubMed/NCBI
17	Xie F, Li Y, Wang M, Huang C, Tao D, Zheng F, Zhang H, Zeng F, Xiao X and Jiang G: Circular RNA BCRC-3 suppresses bladder cancer proliferation through miR-182-5p/p27 axis. Mol Cancer. 17:1442018. View Article : Google Scholar : PubMed/NCBI
18	Gou Q, Wu K, Zhou JK, Xie Y, Liu L and Peng Y: Profiling and bioinformatic analysis of circular RNA expression regulated by c-Myc. Oncotarget. 8:71587–71596. 2017. View Article : Google Scholar : PubMed/NCBI
19	Zhong Z, Lv M and Chen J: Screening differential circular RNA expression profiles reveals the regulatory role of circTCF25-miR-103a-3p/miR-107-CDK6 pathway in bladder carcinoma. Sci Rep. 6:309192016. View Article : Google Scholar : PubMed/NCBI
20	Zhu Z, Xu T, Wang L, Wang X, Zhong S, Xu C and Shen Z: MicroRNA-145 directly targets the insulin-like growth factor receptor I in human bladder cancer cells. FEBS Lett. 588:3180–3185. 2014. View Article : Google Scholar : PubMed/NCBI
21	Wang K, Long B, Liu F, Wang JX, Liu CY, Zhao B, Zhou LY, Sun T, Wang M, Yu T, et al: A circular RNA protects the heart from pathological hypertrophy and heart failure by targeting miR-223. Eur Heart J. 37:2602–2611. 2016. View Article : Google Scholar : PubMed/NCBI
22	Zheng Q, Bao C, Guo W, Li S, Chen J, Chen B, Luo Y, Lyu D, Li Y, Shi G, et al: Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat Commun. 7:112152016. View Article : Google Scholar : PubMed/NCBI
23	Jin P, Huang Y, Zhu P, Zou Y, Shao T and Wang O: CircRNA circHIPK3 serves as a prognostic marker to promote glioma progression by regulating miR-654/IGF2BP3 signaling. Biochem Biophys Res Commun. 503:1570–1574. 2018. View Article : Google Scholar : PubMed/NCBI
24	Li Y, Wan B, Liu L, Zhou L and Zeng Q: Circular RNA circMTO1 suppresses bladder cancer metastasis by sponging miR-221 and inhibiting epithelial-to-mesenchymal transition. Biochem Biophys Res Commun. 508:991–996. 2019. View Article : Google Scholar : PubMed/NCBI