Skip to content
2000
Volume 25, Issue 11
  • ISSN: 1871-5303
  • E-ISSN: 2212-3873

Abstract

Background

Chronic Kidney Disease (CKD) is a common chronic disease that is a threat to human health. Accumulating evidence showed that long noncoding RNAs (lncRNAs) are associated with various diseases and can function as competing endogenous RNAs (ceRNAs). However, the roles and functions of the lncRNA‒miRNA-mRNA network in CKD are still unclear.

Methods

In this study, we performed differential expression analysis of lncRNAs, miRNAs, and mRNAs in CKD using the datasets GSE66494 and GSE80247 from the Gene Expression Omnibus. A total of 33 lncRNAs, 20 miRNAs, and 240 mRNAs were differentially expressed between CKD patients and healthy controls. Two ceRNA interaction modules composed of 11 hub nodes, namely, 2 lncRNAs (LINC01086, LINC01094), 2 miRNAs (hsa-miR-197-3p, hsa-miR-513b-5p) and 7 mRNAs (CENPF, TOP2A, ARHGAP11A, CEP55, MELK, DTL, and ANLN) were constructed. knockdown of LINC01094 expression in renal tubular epithelial HK2 cells significantly attenuated the phenotype of TGFβ1-induced cell fibrosis.

Results

The results of RNA immunoprecipitation (RIP) experiments and dual-luciferase reporter experiments based on constructed mutants confirmed that LINC01094 could mediate MELK expression by sponging miR-513b-5p.

Conclusion

Our observations indicated that lowering the expression of LINC01094 can significantly attenuate the TGFβ1-induced fibrosis phenotype in HK2 cells and renal inflammation through the miR-513b-5p/MELK/Smad3 signalling axis.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/emiddt/10.2174/0118715303306110240820072347
2024-09-23
2025-09-12

  • From This Site

    /content/journals/emiddt/10.2174/0118715303306110240820072347
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. GottliebE.R. EstiverneC. TolanN.V. MelansonS.E.F. MenduM.L. Estimated GFR with cystatin C and creatinine in clinical practice: A retrospective cohort study.Kidney Med.20235310060010.1016/j.xkme.2023.100600 36879723
     [Google Scholar]
  2. XieY. BoweB. MokdadA.H. XianH. YanY. LiT. MaddukuriG. TsaiC.Y. FloydT. Al-AlyZ. Analysis of the Global Burden of Disease study highlights the global, regional, and national trends of chronic kidney disease epidemiology from 1990 to 2016.Kidney Int.201894356758110.1016/j.kint.2018.04.011 30078514
     [Google Scholar]
  3. LiuY. HeQ. LiQ. TianM. LiX. YaoX. HeD. DengC. Global incidence and death estimates of chronic kidney disease due to hypertension from 1990 to 2019, an ecological analysis of the global burden of diseases 2019 study.BMC Nephrol.202324135210.1186/s12882‑023‑03391‑z 38031057
     [Google Scholar]
  4. RomagnaniP. RemuzziG. GlassockR. LevinA. JagerK.J. TonelliM. MassyZ. WannerC. AndersH.J. Chronic kidney disease.Nat. Rev. Dis. Primers2017311708810.1038/nrdp.2017.88 29168475
     [Google Scholar]
  5. SalmenaL. PolisenoL. TayY. KatsL. PandolfiP.P. A ceRNA hypothesis: The rosetta stone of a hidden RNA language?Cell2011146335335810.1016/j.cell.2011.07.014 21802130
     [Google Scholar]
  6. TayY. RinnJ. PandolfiP.P. The multilayered complexity of ceRNA crosstalk and competition.Nature2014505748334435210.1038/nature12986 24429633
     [Google Scholar]
  7. NemethK. BayraktarR. FerracinM. CalinG.A. Non-coding RNAs in disease: From mechanisms to therapeutics.Nat. Rev. Genet.2023202337968332 37968332
     [Google Scholar]
  8. WangJ. SuZ. LuS. FuW. LiuZ. JiangX. LncRNA HOXA-AS2 and its molecular mechanisms in human cancer.Clin. Chim. Acta2018485229233
     [Google Scholar]
  9. LuaibiA.R. Al-SaffarM. JalilA.T. RasolM.A. FedorovichE.V. SalehM.M. AhmedO.S. Long non-coding RNAs: The modulators of innate and adaptive immune cells.Pathol. Res. Pract.202324115429510.1016/j.prp.2022.154295 36608622
     [Google Scholar]
  10. GiannuzziF. MaiullariS. GesualdoL. SallustioF. The mission of long non-coding RNAs in human adult renal stem/progenitor cells and renal diseases.Cells2023128111510.3390/cells12081115 37190024
     [Google Scholar]
  11. LoganathanT. Doss CG.P. Non-coding RNAs in human health and disease: Potential function as biomarkers and therapeutic targets.Funct. Integr. Genomics20232313310.1007/s10142‑022‑00947‑4 36625940
     [Google Scholar]
  12. ThomsonD.W. DingerM.E. Endogenous microRNA sponges: Evidence and controversy.Nat. Rev. Genet.201617527228310.1038/nrg.2016.20 27040487
     [Google Scholar]
  13. MattickJ.S. AmaralP.P. CarninciP. CarpenterS. ChangH.Y. ChenL.L. ChenR. DeanC. DingerM.E. FitzgeraldK.A. GingerasT.R. GuttmanM. HiroseT. HuarteM. JohnsonR. KanduriC. KapranovP. LawrenceJ.B. LeeJ.T. MendellJ.T. MercerT.R. MooreK.J. NakagawaS. RinnJ.L. SpectorD.L. UlitskyI. WanY. WiluszJ.E. WuM. Long non-coding RNAs: Definitions, functions, challenges and recommendations.Nat. Rev. Mol. Cell Biol.202324643044710.1038/s41580‑022‑00566‑8 36596869
     [Google Scholar]
  14. KouhsarM. Azimzadeh JamalkandiS. MoeiniA. Masoudi-NejadA. Detection of novel biomarkers for early detection of Non-muscle-invasive bladder Cancer using competing endogenous RNA network analysis.Sci. Rep.201991843410.1038/s41598‑019‑44944‑3 31182759
     [Google Scholar]
  15. LiG. XuX. YangL. CaiY. SunY. GuoJ. LinY. HuY. ChenM. LiH. WuS. Exploring the association between circRNA expression and pediatric obesity based on a case–control study and related bioinformatics analysis.BMC Pediatr.202323156110.1186/s12887‑023‑04261‑1 37957626
     [Google Scholar]
  16. YangS. WangX. ZhouX. HouL. WuJ. ZhangW. LiH. GaoC. SunC. ncRNA-mediated ceRNA regulatory network: Transcriptomic insights into breast cancer progression and treatment strategies.Biomed. Pharmacother.202316211469810.1016/j.biopha.2023.114698 37060661
     [Google Scholar]
  17. AleksanderS.A. BalhoffJ. CarbonS. CherryJ.M. DrabkinH.J. EbertD. FeuermannM. GaudetP. HarrisN.L. HillD.P. LeeR. MiH. MoxonS. MungallC.J. MuruganuganA. MushayahamaT. SternbergP.W. ThomasP.D. Van AukenK. RamseyJ. SiegeleD.A. ChisholmR.L. FeyP. AspromonteM.C. NugnesM.V. QuagliaF. TosattoS. GiglioM. NadendlaS. AntonazzoG. AttrillH. dos SantosG. MarygoldS. StreletsV. TaboneC.J. ThurmondJ. ZhouP. AhmedS.H. AsanitthongP. Luna BuitragoD. ErdolM.N. GageM.C. Ali KadhumM. LiK.Y.C. LongM. MichalakA. PesalaA. PritazahraA. SaverimuttuS.C.C. SuR. ThurlowK.E. LoveringR.C. LogieC. OliferenkoS. BlakeJ. ChristieK. CorbaniL. DolanM.E. DrabkinH.J. HillD.P. NiL. SitnikovD. SmithC. CuzickA. SeagerJ. CooperL. ElserJ. JaiswalP. GuptaP. JaiswalP. NaithaniS. Lera-RamirezM. RutherfordK. WoodV. De PonsJ.L. DwinellM.R. HaymanG.T. KaldunskiM.L. KwitekA.E. LaulederkindS.J.F. TutajM.A. VediM. WangS.J. D’EustachioP. AimoL. AxelsenK. BridgeA. Hyka-NouspikelN. MorgatA. AleksanderS.A. CherryJ.M. EngelS.R. KarraK. MiyasatoS.R. NashR.S. SkrzypekM.S. WengS. WongE.D. BakkerE. BerardiniT.Z. ReiserL. AuchinclossA. AxelsenK. Argoud-PuyG. BlatterM.C. BoutetE. BreuzaL. BridgeA. Casals-CasasC. CoudertE. EstreicherA. Livia FamigliettiM. FeuermannM. GosA. Gruaz-GumowskiN. HuloC. Hyka-NouspikelN. JungoF. Le MercierP. LieberherrD. MassonP. MorgatA. PedruzziI. PourcelL. PouxS. RivoireC. SundaramS. BatemanA. Bowler-BarnettE. Bye-A-JeeH. DennyP. IgnatchenkoA. IshtiaqR. LockA. LussiY. MagraneM. MartinM.J. OrchardS. RaposoP. SperettaE. TyagiN. WarnerK. ZaruR. DiehlA.D. LeeR. ChanJ. DiamantakisS. RacitiD. ZarowieckiM. FisherM. James-ZornC. PonferradaV. ZornA. RamachandranS. RuzickaL. WesterfieldM. AleksanderS.A. BalhoffJ. CarbonS. CherryJ.M. DrabkinH.J. EbertD. FeuermannM. GaudetP. HarrisN.L. HillD.P. LeeR. MiH. MoxonS. MungallC.J. MuruganuganA. MushayahamaT. SternbergP.W. ThomasP.D. Van AukenK. RamseyJ. SiegeleD.A. ChisholmR.L. FeyP. AspromonteM.C. NugnesM.V. QuagliaF. TosattoS. GiglioM. NadendlaS. AntonazzoG. AttrillH. dos SantosG. MarygoldS. StreletsV. TaboneC.J. ThurmondJ. ZhouP. AhmedS.H. AsanitthongP. Luna BuitragoD. ErdolM.N. GageM.C. Ali KadhumM. LiK.Y.C. LongM. MichalakA. PesalaA. PritazahraA. SaverimuttuS.C.C. SuR. ThurlowK.E. LoveringR.C. LogieC. OliferenkoS. BlakeJ. ChristieK. CorbaniL. DolanM.E. DrabkinH.J. HillD.P. NiL. SitnikovD. SmithC. CuzickA. SeagerJ. CooperL. ElserJ. JaiswalP. GuptaP. JaiswalP. NaithaniS. Lera-RamirezM. RutherfordK. WoodV. De PonsJ.L. DwinellM.R. HaymanG.T. KaldunskiM.L. KwitekA.E. LaulederkindS.J.F. TutajM.A. VediM. WangS-J. D’EustachioP. AimoL. AxelsenK. BridgeA. Hyka-NouspikelN. MorgatA. AleksanderS.A. CherryJ.M. EngelS.R. KarraK. MiyasatoS.R. NashR.S. SkrzypekM.S. WengS. WongE.D. BakkerE. BerardiniT.Z. ReiserL. AuchinclossA. AxelsenK. Argoud-PuyG. BlatterM-C. BoutetE. BreuzaL. BridgeA. Casals-CasasC. CoudertE. EstreicherA. Livia FamigliettiM. FeuermannM. GosA. Gruaz-GumowskiN. HuloC. Hyka-NouspikelN. JungoF. Le MercierP. LieberherrD. MassonP. MorgatA. PedruzziI. PourcelL. PouxS. RivoireC. SundaramS. BatemanA. Bowler-BarnettE. Bye-A-JeeH. DennyP. IgnatchenkoA. IshtiaqR. LockA. LussiY. MagraneM. MartinM.J. OrchardS. RaposoP. SperettaE. TyagiN. WarnerK. ZaruR. DiehlA.D. LeeR. ChanJ. DiamantakisS. RacitiD. ZarowieckiM. FisherM. James-ZornC. PonferradaV. ZornA. RamachandranS. RuzickaL. WesterfieldM. The gene ontology knowledgebase in 2023.Genetics20232241iyad03110.1093/genetics/iyad031 36866529
     [Google Scholar]
  18. SunQ. BaiL. ZhuS. ChengL. XuY. CaiY.D. ChenH. ZhangJ. Analysis of lymphoma-related genes with gene ontology and kyoto encyclopedia of genes and genomes enrichment.BioMed Res. Int.202220221810.1155/2022/8503511 35795312
     [Google Scholar]
  19. MaZ. ZhongP. YueP. SunZ. Identification of immune-related molecular markers in intracranial aneurysm (IA) based on machine learning and cytoscape-cytohubba plug-in.BMC Genomic Data20232412010.1186/s12863‑023‑01121‑w 37041519
     [Google Scholar]
  20. LiG. HanL. RenF. ZhangR. QinG. Prognostic value of the tumor‐specific ceRNA network in epithelial ovarian cancer.J. Cell. Physiol.201923412220712208110.1002/jcp.28770 31152442
     [Google Scholar]
  21. ZhangY. LiZ. WuH. WangJ. ZhangS. Esculetin alleviates murine lupus nephritis by inhibiting complement activation and enhancing Nrf2 signaling pathway.J. Ethnopharmacol.202228811500410.1016/j.jep.2022.115004 35051603
     [Google Scholar]
  22. ZhangS. XinH. LiY. ZhangD. ShiJ. YangJ. ChenX. Skimmin, a coumarin from Hydrangea paniculata, slows down] the progression of membranous glomerulonephritis by anti-inflammatory effects and inhibiting immune complex deposition.Evid. Based Complement. Alternat. Med.20132013819296 23990847
     [Google Scholar]
  23. WangW. ShengL. ChenY. LiZ. WuH. MaJ. ZhangD. ChenX. ZhangS. Total coumarin derivates from Hydrangea paniculata attenuate renal injuries in cationized-BSA induced membranous nephropathy by inhibiting complement activation and interleukin 10-mediated interstitial fibrosis.Phytomedicine20229615388610.1016/j.phymed.2021.153886 35026512
     [Google Scholar]
  24. SeongH.A. JungH. HaH. Murine protein serine/threonine kinase 38 stimulates TGF-beta signaling in a kinase-dependent manner via direct phosphorylation of Smad proteins.J. Biol. Chem.201028540309593097010.1074/jbc.M110.138370 20659902
     [Google Scholar]
  25. KovesdyC.P. Epidemiology of chronic kidney disease: An update 2022.Kidney Int.2022121711
     [Google Scholar]
  26. PradhanN. DobreM. Emerging preventive strategies in chronic kidney disease: Recent evidence and gaps in knowledge.Curr. Atheroscler. Rep.202325121047105810.1007/s11883‑023‑01172‑5 38038822
     [Google Scholar]
  27. LoR. NarasakiY. LeiS. RheeC.M. Management of traditional risk factors for the development and progression of chronic kidney disease.Clin. Kidney J.202316111737175010.1093/ckj/sfad101 37915906
     [Google Scholar]
  28. AbbaszadehM. KarimiM. RajaeiS. The landscape of non-coding RNAs in the immunopathogenesis of Endometriosis.Front. Immunol.202314122382810.3389/fimmu.2023.1223828 37675122
     [Google Scholar]
  29. HusseinR.M. Long non-coding RNAs: The hidden players in diabetes mellitus-related complications.Diabetes Metab. Syndr.2023171010287210.1016/j.dsx.2023.102872 37797393
     [Google Scholar]
  30. JainM. ZhangL. HeM. ZhangY.Q. ShenM. KebebewE. TOP2A is overexpressed and is a therapeutic target for adrenocortical carcinoma.Endocr. Relat. Cancer201320336137010.1530/ERC‑12‑0403 23533247
     [Google Scholar]
  31. GaoZ. ManX. LiZ. BiJ. LiuX. LiZ. ZhuY. ZhangZ. KongC. Expression profiles analysis identifies the values of carcinogenesis and the prognostic prediction of three genes in adrenocortical carcinoma.Oncol. Rep.20194142440245210.3892/or.2019.7021 30816525
     [Google Scholar]
  32. GuoJ. GuY. MaX. ZhangL. LiH. YanZ. HanY. XieL. GuoX. Identification of hub genes and pathways in adrenocortical carcinoma by integrated bioinformatic analysis.J. Cell. Mol. Med.20202484428443810.1111/jcmm.15102 32147961
     [Google Scholar]
  33. ChenD. MaruschkeM. HakenbergO. ZimmermannW. StiefC.G. BuchnerA. TOP2A, HELLS, ATAD2, and TET3 are novel prognostic markers in renal cell carcinoma.Urology2017102265.e1265.e7
     [Google Scholar]
  34. LanJ. HuangH.Y. LeeS.W. ChenT.J. TaiH.C. HsuH.P. ChangK.Y. LiC.F. TOP2A overexpression as a poor prognostic factor in patients with nasopharyngeal carcinoma.Tumour Biol.201435117918710.1007/s13277‑013‑1022‑6 23897556
     [Google Scholar]
  35. de ResendeM.F. VieiraS. ChinenL.T.D. ChiappelliF. da FonsecaF.P. GuimarãesG.C. SoaresF.A. NevesI. PagottyS. PellioniszP.A. BarkhordarianA. BrantX. RochaR.M. Prognostication of prostate cancer based on TOP2A protein and gene assessment: TOP2A in prostate cancer.J. Transl. Med.20131113610.1186/1479‑5876‑11‑36 23398928
     [Google Scholar]
  36. ChanG.K.T. SchaarB.T. YenT.J. Characterization of the kinetochore binding domain of CENP-E reveals interactions with the kinetochore proteins CENP-F and hBUBR1.J. Cell Biol.19981431496310.1083/jcb.143.1.49 9763420
     [Google Scholar]
  37. YangZ.Y. GuoJ. LiN. QianM. WangS.N. ZhuX.L. Mitosin/CENP-F is a conserved kinetochore protein subjected to cytoplasmic dynein-mediated poleward transport.Cell Res.200313427528310.1038/sj.cr.7290172 12974617
     [Google Scholar]
  38. HaleyC.O. WatersA.M. BaderD.M. Malformations in the murine kidney caused by loss of CENP-F function.Anat. Rec. (Hoboken)2019302116317010.1002/ar.24018
     [Google Scholar]
  39. YamadaY. AraiT. KojimaS. SugawaraS. KatoM. OkatoA. YamazakiK. NayaY. IchikawaT. SekiN. Regulation of antitumor miR‐144‐5p targets oncogenes: Direct regulation of syndecan‐3 and its clinical significance.Cancer Sci.201810992919293610.1111/cas.13722 29968393
     [Google Scholar]
  40. ChengY. HongM. ChengB. Identified differently expressed genes in renal cell carcinoma by using multiple microarray datasets running head: Differently expressed genes in renal cell carcinoma.Eur. Rev. Med. Pharmacol. Sci.201418710331040 24763884
     [Google Scholar]
  41. GbadegesinR.A. HallG. AdeyemoA. HankeN. TossidouI. BurchetteJ. WuG. HomstadA. SparksM.A. GomezJ. JiangR. AlonsoA. LavinP. ConlonP. KorstanjeR. StanderM.C. ShamsanG. BaruaM. SpurneyR. SinghalP.C. KoppJ.B. HallerH. HowellD. PollakM.R. ShawA.S. SchifferM. WinnM.P. Mutations in the gene that encodes the F-actin binding protein anillin cause FSGS.J. Am. Soc. Nephrol.20142591991200210.1681/ASN.2013090976 24676636
     [Google Scholar]
  42. ChenH. ZhuD. ZhengZ. CaiY. ChenZ. XieW. CEP55 promotes epithelial-mesenchymal transition in renal cell carcinoma through PI3K/AKT/mTOR pathway.Clin. Transl. Oncol.2019217939949
     [Google Scholar]
  43. ZhouL. LiuS. LiX. YinM. LiS. LongH. Diagnostic and prognostic value of CEP55 in clear cell renal cell carcinoma as determined by bioinformatics analysis.Mol. Med. Rep.20191953485349610.3892/mmr.2019.10042 30896867
     [Google Scholar]
  44. LiuL. XuQ. XiongY. DengH. ZhouJ. LncRNA LINC01094 contributes to glioma progression by modulating miR-224-5p/CHSY1 axis.Hum. Cell202135121422510.1007/s13577‑021‑00637‑6 34716872
     [Google Scholar]
  45. JiangY. LiW. YanY. YaoX. GuW. ZhangH. LINC01094 triggers radio-resistance in clear cell renal cell carcinoma via miR-577/CHEK2/FOXM1 axis.Cancer Cell Int.202020127410.1186/s12935‑020‑01306‑8 32595418
     [Google Scholar]
  46. XuH. WangX. WuJ. JiH. ChenZ. GuoH. HouJ. Long non-coding RNA LINC01094 Promotes the development of clear cell renal cell carcinoma by upregulating SLC2A3 via MicroRNA-184.Front. Genet.20201156296710.3389/fgene.2020.562967 33173535
     [Google Scholar]
  47. YingminM. ZheH. YunjianZ. YuqiZ. Zili S. LINC01094 accelerates the metastasis of hepatocellular carcinoma via the miR-26b-3p/MDM4 axis.Cell. Mol. Biol.202369618118510.14715/cmb/2023.69.6.27 37605571
     [Google Scholar]
  48. GongZ. ZhangY. YangY. YangY. ZhangJ. WangY. ZhaoL. YuN. WuZ. GuoW. LncRNA LINC01094 promotes cells proliferation and metastasis through the PTEN/AKT pathway by targeting AZGP1 in gastric cancer.Cancers (Basel)2023154126110.3390/cancers15041261 36831602
     [Google Scholar]
  49. HuangS. LiangS. HuangJ. LuoP. MoD. WangH. LINC01806 mediated by STAT1 promotes cell proliferation, migration, invasion, and stemness in non-small cell lung cancer through Notch signaling by miR-4428/NOTCH2 axis.Cancer Cell Int.202222119810.1186/s12935‑022‑02560‑8 35599309
     [Google Scholar]
  50. OshiM. GandhiS. HuyserM.R. TokumaruY. YanL. YamadaA. MatsuyamaR. EndoI. TakabeK. MELK expression in breast cancer is associated with infiltration of immune cell and pathological compete response (pCR) after neoadjuvant chemotherapy.Am. J. Cancer Res.202111944214437 34659896
     [Google Scholar]
  51. ThangarajK. PonnusamyL. NatarajanS.R. ManoharanR. MELK/MPK38 in cancer: From mechanistic aspects to therapeutic strategies.Drug Discov. Today202025122161217310.1016/j.drudis.2020.09.029 33010478
     [Google Scholar]
  52. SeongH.A. ManoharanR. HaH. Smad proteins differentially regulate obesity-induced glucose and lipid abnormalities and inflammation via class-specific control of AMPK-related kinase MPK38/MELK activity.Cell Death Dis.20189547110.1038/s41419‑018‑0489‑x 29700281
     [Google Scholar]
/content/journals/emiddt/10.2174/0118715303306110240820072347
Loading
LINCRNA01094 Promotes Renal Interstitial Fibrosis via the Mir-513b-5p/MELK/Smad3 Axis
Endocr Metab Immune Disord Drug Targets 25, 879 (2025); https://doi.org/10.2174/0118715303306110240820072347
/content/journals/emiddt/10.2174/0118715303306110240820072347
/content/journals/emiddt/10.2174/0118715303306110240820072347
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s website along with the published article. Table S1: The co-expressed 273 differentially expressed RNAs in the GSE66494-Validation and Discovery datasets and 20 differentially expressed miRNAs in the GSE80247 dataset. Table : GO functional and KEGG pathway enrichment analyses of the 131 upregulated and 109 downregulated differentially expressed mRNAs.

file format download Download

  • Article Type:     Research Article
Keyword(s): bioinformatics analysis; Chronic kidney disease; competing endogenous RNA network; LINC01094; long noncoding RNA; MELK

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test