Multi-Omics Characterization of Circular RNA-Encoded Novel Proteins Associated With Bladder Outlet Obstruction

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2022 Jan 24

PMID 35071227

Authors

Baoyi Zhu

Zhanfang Kang

Sihua Zhu

Yuying Zhang

Xiangmao Lai

Lilin Zhou

Hai Huang

Xiaofeng Gao

Chonghe Jiang

Jianwen Zeng

Affiliations

Soon will be listed here.

Abstract

Bladder outlet obstruction (BOO) is a common urologic disease associated with poorly understood molecular mechanisms. This study aimed to investigate the possible involvements of circRNAs (circular RNAs) and circRNA-encoded proteins in BOO development. The rat BOO model was established by the partial bladder outlet obstruction surgery. Differential expression of circRNA and protein profiles were characterized by deep RNA sequencing and iTRAQ quantitative proteomics respectively. Novel proteins encoded by circRNAs were predicted through ORF (open reading frame) selection using the GETORF software and verified by the mass spectrometry in proteomics, combined with the validation of their expressional alterations by quantitative RT-PCR. Totally 3,051 circRNAs were differentially expressed in bladder tissues of rat BOO model with widespread genomic distributions, including 1,414 up-regulated, and 1,637 down-regulated circRNAs. Our following quantitative proteomics revealed significant changes of 85 proteins in rat BOO model, which were enriched in multiple biological processes and signaling pathways such as the PPAR and Wnt pathways. Among them, 21 differentially expressed proteins were predicted to be encoded by circRNAs and showed consistent circRNA and protein levels in rat BOO model. The expression levels of five protein-encoding circRNAs were further validated by quantitative RT-PCR and mass spectrometry. The circRNA and protein profiles were substantially altered in rat BOO model, with great expressional changes of circRNA-encoded novel proteins.

Citing Articles

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References

Huang G, Liang M, Liu H, Huang J, Li P, Wang C . CircRNA hsa_circRNA_104348 promotes hepatocellular carcinoma progression through modulating miR-187-3p/RTKN2 axis and activating Wnt/β-catenin pathway. Cell Death Dis. 2020; 11(12):1065. PMC: 7734058. DOI: 10.1038/s41419-020-03276-1. View

Legnini I, Di Timoteo G, Rossi F, Morlando M, Briganti F, Sthandier O . Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis. Mol Cell. 2017; 66(1):22-37.e9. PMC: 5387670. DOI: 10.1016/j.molcel.2017.02.017. View

Zhang L, Liu C, Dong S . PipeMEM: A Framework to Speed Up BWA-MEM in Spark with Low Overhead. Genes (Basel). 2019; 10(11). PMC: 6896194. DOI: 10.3390/genes10110886. View

Garg M, Maurya N . WNT/β-catenin signaling in urothelial carcinoma of bladder. World J Nephrol. 2019; 8(5):83-94. PMC: 6794554. DOI: 10.5527/wjn.v8.i5.83. View

Saw P, Xu X, Chen J, Song E . Non-coding RNAs: the new central dogma of cancer biology. Sci China Life Sci. 2020; 64(1):22-50. DOI: 10.1007/s11427-020-1700-9. View

Jiang T, Xia Y, Lv J, Li B, Li Y, Wang S . A novel protein encoded by circMAPK1 inhibits progression of gastric cancer by suppressing activation of MAPK signaling. Mol Cancer. 2021; 20(1):66. PMC: 8034133. DOI: 10.1186/s12943-021-01358-y. View

Matsui M, Corey D . Non-coding RNAs as drug targets. Nat Rev Drug Discov. 2016; 16(3):167-179. PMC: 5831170. DOI: 10.1038/nrd.2016.117. View

Gao L, Wang Q, Ren W, Zheng J, Li S, Dou Z . The RBP1-CKAP4 axis activates oncogenic autophagy and promotes cancer progression in oral squamous cell carcinoma. Cell Death Dis. 2020; 11(6):488. PMC: 7316825. DOI: 10.1038/s41419-020-2693-8. View

Li M, Liu Y, Zhang X, Liu J, Wang P . Transcriptomic analysis of high-throughput sequencing about circRNA, lncRNA and mRNA in bladder cancer. Gene. 2018; 677:189-197. DOI: 10.1016/j.gene.2018.07.041. View

10.

Ekman M, Albinsson S, Uvelius B, Sward K . MicroRNAs in Bladder Outlet Obstruction: Relationship to Growth and Matrix Remodelling. Basic Clin Pharmacol Toxicol. 2015; 119 Suppl 3:5-17. DOI: 10.1111/bcpt.12534. View

11.

Meier K, Padmanabhan P . Female bladder outlet obstruction: an update on diagnosis and management. Curr Opin Urol. 2016; 26(4):334-41. DOI: 10.1097/MOU.0000000000000303. View

12.

Majima T, Matsukawa Y, Funahashi Y, Kato M, Yamamoto T, Gotoh M . The effect of mirabegron on bladder blood flow in a rat model of bladder outlet obstruction. World J Urol. 2019; 38(8):2021-2027. DOI: 10.1007/s00345-019-02939-9. View

13.

Niemczyk G, Czarzasta K, Radziszewski P, Wlodarski P, Cudnoch-Jedrzejewska A . Pathophysiological effect of bladder outlet obstruction on the urothelium. Ultrastruct Pathol. 2018; 42(3):317-322. DOI: 10.1080/01913123.2018.1462874. View

14.

Fusco F, Creta M, De Nunzio C, Iacovelli V, Mangiapia F, Li Marzi V . Progressive bladder remodeling due to bladder outlet obstruction: a systematic review of morphological and molecular evidences in humans. BMC Urol. 2018; 18(1):15. PMC: 5844070. DOI: 10.1186/s12894-018-0329-4. View

15.

Liu F, Zhang H, Xie F, Tao D, Xiao X, Huang C . Hsa_circ_0001361 promotes bladder cancer invasion and metastasis through miR-491-5p/MMP9 axis. Oncogene. 2019; 39(8):1696-1709. DOI: 10.1038/s41388-019-1092-z. View

16.

King A, Goldman H . Bladder outlet obstruction in women: functional causes. Curr Urol Rep. 2014; 15(9):436. DOI: 10.1007/s11934-014-0436-z. View

17.

Ding L, Wang R, Shen D, Cheng S, Wang H, Lu Z . Role of noncoding RNA in drug resistance of prostate cancer. Cell Death Dis. 2021; 12(6):590. PMC: 8187453. DOI: 10.1038/s41419-021-03854-x. View

18.

Glazar P, Papavasileiou P, Rajewsky N . circBase: a database for circular RNAs. RNA. 2014; 20(11):1666-70. PMC: 4201819. DOI: 10.1261/rna.043687.113. View

19.

Li J, Xu Q, Huang Z, Mao N, Lin Z, Cheng L . CircRNAs: a new target for the diagnosis and treatment of digestive system neoplasms. Cell Death Dis. 2021; 12(2):205. PMC: 7904779. DOI: 10.1038/s41419-021-03495-0. View

20.

Guo X, Sun F, Chen J, Wang Y, Pan Q, Fan J . circRNA_0046366 inhibits hepatocellular steatosis by normalization of PPAR signaling. World J Gastroenterol. 2018; 24(3):323-337. PMC: 5776394. DOI: 10.3748/wjg.v24.i3.323. View