Generic placeholder image

Combinatorial Chemistry & High Throughput Screening


ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

RNA Seq and ceRNA Network Analysis of the Rat Model of Chronic Kidney Disease

Author(s): Hepeng Xu, Zhen He, Mengjuan Zhang, Wenping Zhou, Chang Xu, Ming He, Zheng Wang* and Xiangting Wang*

Volume 26, Issue 1, 2023

Published on: 31 May, 2022

Page: [116 - 125] Pages: 10

DOI: 10.2174/1386207325666220516145502

Price: $65


Background: Long non-coding RNAs (lncRNAs) containing microRNA (miRNA) response elements (MREs) can be used as competitive endogenous RNAs (ceRNAs) to regulate gene expression.

Objective: The purpose of this study was to investigate the expression profile and role of mRNAs and lncRNAs in unilateral ureteral obstruction (UUO) model rats and to explore any associated competing endogenous (ceRNA) network.

Methods: Using the UUO model, the obstructed kidney was collected on the 15th day after surgery. RNA Seq analysis was performed on renal tissues of four UUO rats and four sham rats. Four mRNAs and four lncRNAs of differentially expressed genes were randomly selected for real-time quantitative PCR (RT qPCR) analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed, and bioinformatics was used to predict MREs. By screening for ceRNAs combined with target gene prediction, a related ceRNA network was constructed and verified by RT-qPCR.

Results: We identified 649 up-regulated lncRNAs, 518 down-regulated lncRNAs, 924 downregulated mRNAs and 2029 up-regulated mRNAs. We identified 30 pathways with the highest enrichment in GO and KEGG. According to the RNA Seq results and the expression of Nr4a1, the network was constructed based on Nr4a1 and included two MREs and ten lncRNAs. Furthermore, lncNONRATT011668.2/miR-361-3p/Nr4a1 was identified and verified according to ceRNA sequencing and target gene prediction.

Conclusion: mRNAs and lncRNAs are differentially expressed in UUO model rats, which may be related to the pathogenesis of chronic kidney disease. The lncNONRATT011668.2/miR-361- 3p/Nr4a1 ceRNA network may be involved in the pathogenesis of chronic kidney disease.

Keywords: ceRNA network, chronic kidney disease, lncRNAs, mRNAs, unilateral ureteral obstruction, gene ontology.

Global, regional, and national burden of chronic kidney disease, 1990-2017: A systematic analysis for the Global Bur-den of Disease Study 2017. LANCET, 2020, 395(10225), 709-733.
Zhang, L.; Wang, F.; Wang, L.; Wang, W.; Liu, B.; Liu, J. Preva-lence of chronic kidney disease in China: A cross-sectional survey. Lancet, 2012, 379(9818), 815-822.
Sandsmark, D.K.; Kasner, S.E. Response to letter regarding article, “proteinuria, but not egfr, predicts stroke risk in chronic kidney disease: chronic renal insufficiency cohort study”. Stroke, 2015, 46(11), e240.
[] [PMID: 26463697]
Welker, M.W.; Weiler, N.; Bechstein, W.O.; Herrmann, E.; Betz, C.; Schöffauer, M.; Zeuzem, S.; Sarrazin, C.; Amann, K.; Jung, O. Key role of renal biopsy in management of pro-gressive chronic kidney disease in liver graft recipients. J. Nephrol., 2019, 32(1), 129-137.
[] [PMID: 29946864]
Duffield, J.S. Cellular and molecular mechanisms in kidney fibrosis. J. Clin. Invest., 2014, 124(6), 2299-2306.
Yu, H.X.; Lin, W.; Yang, K.; Wei, L.J.; Chen, J.L.; Liu, X.Y. Transcriptome-based network analysis reveals hirudin poten-tiates anti-renal fibrosis efficacy in UUO rats. Front. Pharmacol., 2021, 12, 741801.
Huang, J.; Zhang, Z.; Liu, B.; Gao, Y.; Nie, J.; Wen, S. Identi-fication of circular RNA expression profiles in renal fibrosis induced by obstructive injury. Ren. Fail., 2021, 43(1), 1368-1377.
Burris, T.P.; Busby, S.A.; Griffin, P.R. Targeting orphan nu-clear receptors for treatment of metabolic diseases and auto-immunity. Chem. Biol., 2012.
Mohan, H.M.; Aherne, C.M.; Rogers, A.C.; Baird, A.W.; Win-ter, D.C.; Murphy, E.P. Molecular pathways: the role of NR4A orphan nuclear receptors in cancer. Clin. Cancer Res., 2012, 18(12), 3223-3228.
Ikushima, H.; Miyazono, K. TGFbeta signalling: A complex web in cancer progression. Nat. Rev. Cancer, 2010, 10(6), 415-424.
Vervoort, S.J.; Lourenco, A.R.; van Boxtel, R.; Coffer, P.J. SOX4 mediates TGF-beta-induced expression of mesenchymal markers during mammary cell epithelial to mesenchymal transition. PLoS One, 2013, 20(13), 3276.
Ignarski, M.; Islam, R.; Müller, R.U. Long non-coding RNAs in kidney disease. Int. J. Mol. Sci., 2019, 20(13), 3276.
[] [PMID: 31277300]
Kopp, F.; Mendell, J.T. Functional classification and experi-mental dissection of long noncoding RNAs. Cell, 2018, 172(3), 393-407.
Noh, J.H.; Kim, K.M.; McClusky, W.G.; Abdelmohsen, K.; Gorospe, M. Cytoplasmic functions of long noncoding RNAs. Wiley Interdiscip. Rev. RNA, 2018, 9(3), e1471.
Salamon, I.; Saccani Jotti, G.; Condorelli, G. The long noncoding RNA landscape in cardiovascular disease: A brief update. Curr. Opin. Cardiol., 2018, 33(3), 282-289.
[] [PMID: 29543669]
Samudyata; Castelo-Branco, G.; Bonetti, A. Birth, coming of age and death: The intriguing life of long noncoding RNAs. Semin. Cell Dev. Biol., 2018, 79, 143-152.
Hughes, J.; Johnson, R.J. Role of Fas (CD95) in tubulointer-stitial disease induced by unilateral ureteric obstruction. Am. J. Physiol., 1999, 277(1), F26-F32.
Salmena, L.; Poliseno, L.; Tay, Y.; Kats, L.; Pandolfi, P.P. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA lan-guage? Cell, 2011, 146(3), 353-358.
Moriya, Y.; Itoh, M.; Okuda, S.; Yoshizawa, A.C.; Kanehisa, M. KAAS: An automatic genome annotation and pathway reconstruction server. Nucleic Acids Res., 2007, 35(Web Server issue), W182-5.
Rice, P.; Longden, I.; Bleasby, A. EMBOSS: The european molecular biology open software suite. Trends Genet., 2000, 16(6), 279-7.
Zhang, H.F.; Wang, Y.L.; Gao, C.; Gu, Y.T.; Huang, J.; Wang, J.H. Salvianolic acid A attenuates kidney injury and inflam-mation by inhibiting NF-kappaB and p38 MAPK signaling pathways in 5/6 nephrectomized rats. Acta Pharmacol. Sin., 2018, 39(12), 1855-1864.
Wang, M.; Hu, R.; Wang, Y.; Liu, L.; You, H.; Zhang, J. At-ractylenolide III attenuates muscle wasting in chronic kidney disease via the oxidative stress-mediated PI3K/AKT/MTOR pathway. Oxid. Med. Cell. Longev., 2019, 2019, 1875471.
Rayego-Mateos, S.; Valdivielso, J.M. New therapeutic targets in chronic kidney disease progression and renal fibrosis. Expert Opin. Ther. Targets, 2020, 24(7), 655-670.
Liu, Z.G.; Smith, S.W.; McLaughlin, K.A.; Schwartz, L.M.; Osborne, B.A. Apoptotic signals delivered through the T-cell receptor of a T-cell hybrid require the immediate-early gene nur77. Nature, 1994, 367(6460), 281-284.
Schmierer, B.; Hill, C.S. TGFbeta-SMAD signal transduction: Molecular specificity and functional flexibility. Nat. Rev. Mol. Cell Biol., 2007, 8(12), 970-982.
Zhou, F.; Drabsch, Y.; Dekker, T.J.; de Vinuesa, A.G.; Li, Y.; Hawinkels, L.J. Nuclear receptor NR4A1 promotes breast cancer invasion and metastasis by activating TGF-beta signal-ling. Nat. Commun., 2014, 5, 3388.
Kour, S.; Rath, P.C. Long noncoding RNAs in aging and age-related diseases. Ageing Res. Rev., 2016, 26, 1-21.
Song, C.; Zhang, J.; Qi, H.; Feng, C.; Chen, Y.; Cao, Y. The global view of mRNA-related ceRNA cross-talks across car-diovascular diseases. Sci. Rep., 2017, 7(1), 10185.
Wang, J.D.; Zhou, H.S.; Tu, X.X.; He, Y.; Liu, Q.F.; Liu, Q. Prediction of competing endogenous RNA coexpression net-work as prognostic markers in AML. Aging (Albany NY), 2019, 11(10), 3333-3347.
Dong-Yun, S.; Qing-You, X.U.; Xiang-Ting, W.; Xia, W.; Zheng, W.; Cong-Hui, W. Inhibitory effect of eplerenone on cell proliferation in acute cyclosporine nephrotoxicity. Zhongguo Yaolixue Tongbao, 2011, 27(12), 1678-1682.
Duan, L.J.; Ding, M.; Hou, L.J.; Cui, Y.T.; Li, C.J.; Yu, D.M. Long noncoding RNA TUG1 alleviates extracellular matrix accumulation via mediating microRNA-377 targeting of PPARgamma in diabetic nephropathy. Biochem. Biophys. Res. Commun., 2017, 484(3), 598-604.

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy