Top

Published in:

Open Access 01-12-2022 | Research

CircRNA/miRNA/mRNA axis participates in the progression of partial bladder outlet obstruction

Authors: Baoyi Zhu, Jun Gao, Yuying Zhang, Baojian Liao, Sihua Zhu, Chunling Li, Junhao Liao, Jianjia Liu, Chonghe Jiang, Jianwen Zeng

Published in: BMC Urology | Issue 1/2022

Abstract

Background

More and more evidence showed that circRNA/miRNA/mRNA axis played a vital role in the pathogenesis of some diseases. However, the role of circRNA/miRNA/mRNA axis in partial bladder outlet obstruction (pBOO) remains unknown. Our study aimed to explore the complex regulatory mechanism of circRNA/miRNA/mRNA axis in pBOO.

Methods

The pBOO rat model was established, and the bladder tissues were collected for mRNA sequencing. The differentially expressed mRNAs were analyzed by high-throughput sequencing, and the GO and KEGG analysis of the differentially expressed mRNAs were performed. Competing endogenous RNAs (ceRNAs) analysis identified the potential regulation function of circRNA/miRNA/mRNA axis in pBOO. qRT-PCR detected the expression of circRNA/miRNA/mRNA. miRanda software was performed to predict the relationship between circRNA and miRNA, miRNA and mRNA.

Results

Compared with the sham group, a total of 571 mRNAs were differentially expressed in the pBOO group, of which 286 were up-regulated and 285 were down-regulated. GO analysis showed that the mRNAs were mainly involved in cellular process, single-organism process, and cell, etc. KEGG analysis showed that the enriched signaling pathways were metabolic pathways, cell adhesion molecules (CAMs), and HTLV-I infection, etc. Based on the previous transcriptome data and differentially expressed circRNAs, we drew the ceRNA network regulation diagram. qRT-PCR results confirmed that chr3:113195876|113197193/rno-miR-30c-1-3p/Gata4, chr1:126188351|126195625/rno-miR-153-5p/Diaph3, and chr9:81258380|81275269/rno-miR-135b-5p/Pigr axis may have ceRNA function. miRanda confirmed there have the binding sites of circRNA/miRNA/mRNA axis.

Conclusions

CircRNA/miRNA/mRNA axis was involved in the progression of pBOO. Our research on the circRNA/miRNA/mRNA axis revealed new pathogenesis and treatment strategies for pBOO.

Albisinni S, Biaou I, Marcelis Q, Aoun F, De Nunzio C, Roumeguère T. New medical treatments for lower urinary tract symptoms due to benign prostatic hyperplasia and future perspectives. BMC Urol. 2016;16(1):58.PubMedPubMedCentralCrossRef

MacDonald D, McNicholas TA. Drug treatments for lower urinary tract symptoms secondary to bladder outflow obstruction: focus on quality of life. Drugs. 2003;63(18):1947–62.PubMedCrossRef

Kai W, Lin C, Jin Y, Ping-Lin H, Xun L, Bastian A, et al. Urethral meatus stricture BOO stimulates bladder smooth muscle cell proliferation and pyroptosis via IL-1β and the SGK1-NFAT2 signaling pathway. Mol Med Rep. 2020;22(1):219–26.PubMedPubMedCentralCrossRef

Mirone V, Imbimbo C, Longo N, Fusco F. The detrusor muscle: an innocent victim of bladder outlet obstruction. Eur Urol. 2007;51(1):57–66.PubMedCrossRef

Hughes FM Jr, Hill HM, Wood CM, Edmondson AT, Dumas A, Foo WC, et al. The NLRP3 inflammasome mediates inflammation produced by bladder outlet obstruction. J Urol. 2016;195(5):1598–605.PubMedCrossRef

Lin WY, Wu SB, Lin YP, Chang PJ, Levin RM, Wei YH. Reversing bladder outlet obstruction attenuates systemic and tissue oxidative stress. BJU Int. 2012;110(8):1208–13.PubMedCrossRef

Wang N, Duan L, Ding J, Cao Q, Qian S, Shen H, et al. MicroRNA-101 protects bladder of BOO from hypoxia-induced fibrosis by attenuating TGF-β-smad2/3 signaling. IUBMB Life. 2019;71(2):235–43.PubMed

Ghosal S, Das S, Sen R, Chakrabarti J. HumanViCe: host ceRNA network in virus infected cells in human. Front Genet. 2014;5:249.PubMedPubMedCentralCrossRef

Zhou DN, Ye CS, Deng YF. CircRNAs: potency of protein translation and feasibility of novel biomarkers and therapeutic targets for head and neck cancers. Am J Transl Res. 2020;12(5):1535–52.PubMedPubMedCentral

10.

Rong D, Sun H, Li Z, Liu S, Dong C, Fu K, et al. An emerging function of circRNA-miRNAs-mRNA axis in human diseases. Oncotarget. 2017;8(42):73271–81.PubMedPubMedCentralCrossRef

11.

Su Y, Yi Y, Li L, Chen C. circRNA-miRNA-mRNA network in age-related macular degeneration: from construction to identification. Exp Eye Res. 2021;203:108427.PubMedCrossRef

12.

Chen LL. The biogenesis and emerging roles of circular RNAs. Nat Rev Mol Cell Biol. 2016;17(4):205–11.PubMedCrossRef

13.

Wang M, Yu F, Li P. Circular RNAs: characteristics, function and clinical significance in hepatocellular carcinoma. Cancers (Basel). 2018;10(8):258.PubMedCrossRef

14.

Cao M, Zhang L, Wang JH, Zeng H, Peng Y, Zou J, et al. Identifying circRNA-associated-ceRNA networks in retinal neovascularization in mice. Int J Med Sci. 2019;16(10):1356–65.PubMedPubMedCentralCrossRef

15.

Wang B, Wu J, Huang Q, Yuan X, Yang Y, Jiang W, et al. Comprehensive analysis of differentially expressed lncRNA, circRNA and mRNA and their ceRNA networks in mice with severe acute pancreatitis. Front Genet. 2021;12:625846.PubMedPubMedCentralCrossRef

16.

Hrdlickova R, Toloue M, Tian B. RNA-Seq methods for transcriptome analysis. Wiley Interdiscip Rev RNA. 2017;8(1):e1364.CrossRef

17.

Hedlund E, Deng Q. Single-cell RNA sequencing: technical advancements and biological applications. Mol Asp Med. 2018;59:36–46.CrossRef

18.

Monastyrskaya K, Sánchez-Freire V, Hashemi Gheinani A, Klumpp DJ, Babiychuk EB, Draeger A, et al. miR-199a-5p regulates urothelial permeability and may play a role in bladder pain syndrome. Am J Pathol. 2013;182(2):431–48.PubMedCrossRef

19.

Ekman M, Bhattachariya A, Dahan D, Uvelius B, Albinsson S, Swärd K. Mir-29 repression in bladder outlet obstruction contributes to matrix remodeling and altered stiffness. PLoS ONE. 2013;8(12):e82308.PubMedPubMedCentralCrossRef

20.

Zhu B, Kang Z, Zhu S, Zhang Y, Lai X, Zhou L, et al. Multi-omics characterization of circular RNA-encoded novel proteins associated with bladder outlet obstruction. Front Cell Dev Biol. 2022;9:772534.PubMedPubMedCentralCrossRef

21.

Kanno Y, Mitsui T, Kitta T, Moriya K, Tsukiyama T, Hatakeyama S, et al. The inflammatory cytokine IL-1β is involved in bladder remodeling after bladder outlet obstruction in mice. Neurourol Urodyn. 2016;35(3):377–81.PubMedCrossRef

22.

Bschleipfer T, Nandigama R, Moeller S, Illig C, Weidner W, Kummer W. Bladder outlet obstruction influences mRNA expression of cholinergic receptors on sensory neurons in mice. Life Sci. 2012;91(21–22):1077–81.PubMedCrossRef

23.

Patel R, Jain M. NGS QC Toolkit: a toolkit for quality control of next generation sequencing data. PLoS ONE. 2012;7(2):e30619.PubMedPubMedCentralCrossRef

24.

Kim D, Langmead B, Salzberg SL. HISAT: a fast spliced aligner with low memory requirements. Nat Methods. 2015;12(4):357–60.PubMedPubMedCentralCrossRef

25.

Shen S, Kong J, Qiu Y, Yang X, Wang W, Yan L. Identification of core genes and outcomes in hepatocellular carcinoma by bioinformatics analysis. J Cell Biochem. 2019;120(6):10069–81.PubMedCrossRef

26.

Klopfenstein D, Zhang L, Pedersen BS, Ramírez F, Vesztrocy AW, Naldi A, et al. GOATOOLS: a Python library for gene ontology analyses. Sci Rep. 2018;8(1):10872.PubMedPubMedCentralCrossRef

27.

Li C-B, Wang H-F, Feng Z-K, Fu Y-B, Zhang J, Qin J-Y. Identification of immune-related genes for Hepatocellular Carcinoma: a study based on TCGA data. J Men’s Health. 2021;17(2):101–13.CrossRef

28.

Niemczyk G, Fus L, Czarzasta K, Jesion A, Radziszewski P, Gornicka B, et al. Expression of toll-like receptors in the animal model of bladder outlet obstruction. Biomed Res Int. 2020;2020:6632359.PubMedPubMedCentralCrossRef

29.

Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, et al. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495(7441):384–8.PubMedCrossRef

30.

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;677:189–97.PubMedCrossRef

31.

Venø MT, Hansen TB, Venø ST, Clausen BH, Grebing M, Finsen B, et al. Spatio-temporal regulation of circular RNA expression during porcine embryonic brain development. Genome Biol. 2015;16:245.PubMedPubMedCentralCrossRef

32.

Duan LJ, Qi J, Kong XJ, Huang T, Qian XQ, Xu D, et al. MiR-133 modulates TGF-β1-induced bladder smooth muscle cell hypertrophic and fibrotic response: implication for a role of microRNA in bladder wall remodeling caused by bladder outlet obstruction. Cell Signal. 2015;27(2):215–27.PubMedCrossRef

33.

Hashemi Gheinani A, Burkhard FC, Rehrauer H, Aquino Fournier C, Monastyrskaya K. MicroRNA MiR-199a-5p regulates smooth muscle cell proliferation and morphology by targeting WNT2 signaling pathway. J Biol Chem. 2015;290(11):7067–86.PubMedPubMedCentralCrossRef

34.

Duan LJ, Cao QF, Xu D, Liu HL, Qi J. Bioinformatic analysis of microRNA-mRNA expression profiles of bladder tissue induced by bladder outlet obstruction in a rat model. Mol Med Rep. 2017;16(4):4803–10.PubMedCrossRef

35.

Koeck I, Hashemi Gheinani A, Baumgartner U, Vassella E, Bruggmann R, Burkhard FC, et al. Tumor necrosis factor-α initiates miRNA-mRNA signaling cascades in obstruction-induced bladder dysfunction. Am J Pathol. 2018;188(8):1847–64.PubMedCrossRef

36.

Chen W, Yao G, Zhou K. miR-103a-2-5p/miR-30c-1-3p inhibits the progression of prostate cancer resistance to androgen ablation therapy via targeting androgen receptor variant 7. J Cell Biochem. 2019;120(8):14055–64.PubMedCrossRef

37.

Li H, Xu JD, Fang XH, Zhu JN, Yang J, Pan R, et al. Circular RNA circRNA_000203 aggravates cardiac hypertrophy via suppressing miR-26b-5p and miR-140-3p binding to Gata4. Cardiovasc Res. 2020;116(7):1323–34.PubMedCrossRef

38.

Deng ZH, Yu GS, Deng KL, Feng ZH, Huang Q, Pan B, et al. Hsa_circ_0088233 alleviates proliferation, migration, and invasion of prostate cancer by targeting hsa-miR-185-3p. Front Cell Dev Biol. 2020;8:528155.PubMedPubMedCentralCrossRef

39.

Zhang Y, Zhang J, Chen X, Yang Z. Polymeric immunoglobulin receptor (PIGR) exerts oncogenic functions via activating ribosome pathway in hepatocellular carcinoma. Int J Med Sci. 2021;18(2):364–71.PubMedPubMedCentralCrossRef

40.

He Y, Zhang L, Tan F, Wang LF, Liu DH, Wang RJ, et al. MiR-153-5p promotes sensibility of colorectal cancer cells to oxaliplatin via targeting Bcl-2-mediated autophagy pathway. Biosci Biotechnol Biochem. 2020;84(8):1645–51.PubMedCrossRef

41.

Kim J, Morley S, Le M, Bedoret D, Umetsu DT, Di Vizio D, et al. Enhanced shedding of extracellular vesicles from amoeboid prostate cancer cells: potential effects on the tumor microenvironment. Cancer Biol Ther. 2014;15(4):409–18.PubMedPubMedCentralCrossRef

42.

Ren R, Wu J, Zhou MY. MiR-135b-5p affected malignant behaviors of ovarian cancer cells by targeting KDM5B. Eur Rev Med Pharmacol Sci. 2020;24(22):11469.PubMed

43.

Shao L, Chen Z, Soutto M, Zhu S, Lu H, Romero-Gallo J, et al. Helicobacter pylori-induced miR-135b-5p promotes cisplatin resistance in gastric cancer. FASEB J. 2019;33(1):264–74.PubMedCrossRef

Title: CircRNA/miRNA/mRNA axis participates in the progression of partial bladder outlet obstruction
Authors: Baoyi Zhu
Jun Gao
Yuying Zhang
Baojian Liao
Sihua Zhu
Chunling Li
Junhao Liao
Jianjia Liu
Chonghe Jiang
Jianwen Zeng
Publication date: 01-12-2022
Publisher: BioMed Central
Published in: BMC Urology / Issue 1/2022
Electronic ISSN: 1471-2490
DOI: https://doi.org/10.1186/s12894-022-01132-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

CircRNA/miRNA/mRNA axis participates in the progression of partial bladder outlet obstruction

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2022

Epstein–Barr virus infection is associated with the nuclear factor-kappa B p65 signaling pathway in renal cell carcinoma

The SLC6A19 gene mutation in a young man with hyperglycinuria and nephrolithiasis: a case report and literature review

A common tumor in an uncommon site: epithelioid Leiomyoma arising from the seminal vesicle—a case report

Constructing and validating nomograms to predict risk and prognostic factors of distant metastasis in urothelial bladder cancer patients: a population-based retrospective study

Flexible ureteroscopy with ultrasound guidance for the treatment of parapelvic renal cysts: A complementary approach for locating the cystic wall

Novel Gerota-edge-sling technique facilitates retroperitoneal robot-assisted partial nephrectomy: a comparative study