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2000
Volume 25, Issue 6
  • ISSN: 1568-0096
  • E-ISSN: 1873-5576

Abstract

Aim

We aimed to explore the role of urotensin 2 (UTS2) in glioblastoma (GBM).

Background

GBM is the most malignant primary brain cancer with a poor prognosis. Previous studies have suggested that GBM vessels undergo dynamic remodeling modulated by tumor vasodilation and vasoconstriction instead of tumor angiogenesis.

Objective

Here, we have first investigated the expression and function of UTS2, a potent vasoconstrictor, in GBM.

Methods

The mRNA expression profiles and clinical information of GBM patients were obtained from the TCGA database. The clinical relevance of UTS2 was explored by the Mann-Whitney U test and Cox hazard regression survival test. We further explored the role of UTS2 in GBM cell proliferation, migration, and tumor immune microenvironment. Moreover, we established the mice model to validate its oncogenic effects on GBM progression.

Results

Although we did not find significant correlations between UTS2 expression and patients’ clinical characteristics, UTS2 was identified as a valid independent prognostic indicator according to multivariate survival analysis. Knockdown of UTS2 resulted in decreased GBM cell proliferation and migration. In addition, functional enrichment analysis implied UTS2 to be involved in the regulation of the immune microenvironment. studies showed that UTS2 knockdown suppressed GBM xenograft growth, highlighting the tumor-promoting effects of UTS2 on GBM.

Conclusion

Our study identified that UTS2 could predict the prognosis of GBM patients and provided evidence regarding its oncogenic effects both and .

© 2025 Bentham Science Publishers
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2025-08-17

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References

  1. OmuroA. DeAngelisL.M. Glioblastoma and other malignant gliomas: A clinical review.JAMA2013310171842185010.1001/jama.2013.28031924193082
     [Google Scholar]
  2. WenP.Y. ReardonD.A. Progress in glioma diagnosis, classification and treatment.Nat. Rev. Neurol.2016122697010.1038/nrneurol.2015.24226782337
     [Google Scholar]
  3. MelinB.S. Barnholtz-SloanJ.S. WrenschM.R. JohansenC. Il’yasovaD. KinnersleyB. OstromQ.T. LabrecheK. ChenY. ArmstrongG. LiuY. Eckel-PassowJ.E. DeckerP.A. LabussièreM. IdbaihA. Hoang-XuanK. Di StefanoA.L. MokhtariK. DelattreJ.Y. BroderickP. GalanP. GousiasK. SchrammJ. SchoemakerM.J. FlemingS.J. HermsS. HeilmannS. NöthenM.M. WichmannH.E. SchreiberS. SwerdlowA. LathropM. SimonM. SansonM. AnderssonU. RajaramanP. ChanockS. LinetM. WangZ. YeagerM. WienckeJ.K. HansenH. McCoyL. RiceT. KoselM.L. SicotteH. AmosC.I. BernsteinJ.L. DavisF. LachanceD. LauC. MerrellR.T. ShildkrautJ. Ali-OsmanF. SadetzkiS. ScheurerM. SheteS. LaiR.K. ClausE.B. OlsonS.H. JenkinsR.B. HoulstonR.S. BondyM.L. Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors.Nat. Genet.201749578979410.1038/ng.382328346443
     [Google Scholar]
  4. SareenH. MaY. BeckerT.M. RobertsT.L. de SouzaP. PowterB. Molecular biomarkers in glioblastoma: A systematic review and meta-analysis.Int. J. Mol. Sci.20222316883510.3390/ijms2316883536012105
     [Google Scholar]
  5. YeH. WangK. WangM. LiuR. SongH. LiN. LuQ. ZhangW. DuY. YangW. ZhongL. WangY. YuB. WangH. KanQ. ZhangH. WangY. HeZ. SunJ. Bioinspired nanoplatelets for chemo-photothermal therapy of breast cancer metastasis inhibition.Biomaterials201920611210.1016/j.biomaterials.2019.03.02430921730
     [Google Scholar]
  6. YeH. WangK. LuQ. ZhaoJ. WangM. KanQ. ZhangH. WangY. HeZ. SunJ. Nanosponges of circulating tumor-derived exosomes for breast cancer metastasis inhibition.Biomaterials202024211993210.1016/j.biomaterials.2020.11993232169772
     [Google Scholar]
  7. ZhaoJ. YeH. LuQ. WangK. ChenX. SongJ. WangH. LuY. ChengM. HeZ. ZhaiY. ZhangH. SunJ. Inhibition of post-surgery tumour recurrence via a sprayable chemo-immunotherapy gel releasing PD-L1 antibody and platelet-derived small EVs.J. Nanobiotechnology20222016210.1186/s12951‑022‑01270‑735109878
     [Google Scholar]
  8. OrenO. HerrmannJ. Arterial events in cancer patients—the case of acute coronary thrombosis.J. Thorac. Dis.201810S35S4367S438510.21037/jtd.2018.12.7930701104
     [Google Scholar]
  9. ZhangQ. LiuH. ZhuQ. ZhanP. ZhuS. ZhangJ. LvT. SongY. Patterns and functional implications of platelets upon tumor “education”.Int. J. Biochem. Cell Biol.201790688010.1016/j.biocel.2017.07.01828754316
     [Google Scholar]
  10. SuematsuM. NakamuraT. TokumotoY. YamamotoT. KajimuraM. KabeY. CO‐CBS‐H 2 S axis: From vascular mediator to cancer regulator.Microcirculation201623318319010.1111/micc.1225326537442
     [Google Scholar]
  11. CookN. BraisR. QianW. Chan Wah HakC. CorrieP.G. Endothelin-1 and endothelin B receptor expression in pancreatic adenocarcinoma.J. Clin. Pathol.201568430931310.1136/jclinpath‑2014‑20252125572612
     [Google Scholar]
  12. WeydertC. EsserA. MejiaR. DrakeJ. BarnesJ. HenryM. Endothelin-1 inhibits prostate cancer growth in vivo through vasoconstriction of tumor-feeding arterioles.Cancer Biol. Ther.20098872072910.4161/cbt.8.8.792219242129
     [Google Scholar]
  13. SvistunovA.A. TarasovV.V. ShakhmardanovaS.A. SologovaS.S. BagaturiyaE.T. ChubarevV.N. Galenko-YaroshevskyP.A. Avila-RodriguezM.F. BarretoG.E. AlievG. UrotensinI.I. Urotensin II: Molecular mechanisms of biological activity.Curr. Protein Pept. Sci.201819992493410.2174/138920371866617082916233528875851
     [Google Scholar]
  14. AvagimyanA. KajaiaA. GabuniaL. GhambashidzeK. SulashviliN. RatianiL. Heshmat-GhahdarijaniK. SheibaniM. AznauryanA. Urotensin-II as a promising key-point of cardiovascular disturbances sequel.Curr. Probl. Cardiol.202110107410.1016/j.cpcardiol.2021.10107434848248
     [Google Scholar]
  15. GravinaA.G. DallioM. TuccilloC. MartoranoM. AbenavoliL. LuzzaF. StiusoP. LamaS. GriecoP. MerlinoF. CaragliaM. LoguercioC. FedericoA. Urotensin II receptor expression in patients with ulcerative colitis: A pilot study.Minerva Gastroenterol. Dietol.2020661232810.23736/S1121‑421X.19.02602‑331293119
     [Google Scholar]
  16. TakahashiK. TotsuneK. MurakamiO. ShibaharaS. Expression of urotensin II and urotensin II receptor mRNAs in various human tumor cell lines and secretion of urotensin II-like immunoreactivity by SW-13 adrenocortical carcinoma cells.Peptides20012271175117910.1016/S0196‑9781(01)00441‑711445248
     [Google Scholar]
  17. FedericoA. ZappavignaS. DallioM. MissoG. MerlinoF. LoguercioC. NovellinoE. GriecoP. CaragliaM. Urotensin-II receptor: A double identity receptor involved in vasoconstriction and in the development of digestive tract cancers and other tumors.Curr. Cancer Drug Targets201717210912110.2174/156800961666616062110124827338741
     [Google Scholar]
  18. YumrutasO. OztuzcuS. BüyükhatipogluH. BozgeyikI. BozgeyikE. IgciY.Z. BagisH. CevikM.O. KalenderM.E. EslikZ. ArslanA. The role of the UTS2 gene polymorphisms and plasma Urotensin-II levels in breast cancer.Tumour Biol.20153664427443210.1007/s13277‑015‑3082‑225604143
     [Google Scholar]
  19. TakahashiK. TotsuneK. KitamuroT. SoneM. MurakamiO. ShibaharaS. Three vasoactive peptides, endothelin-1, adrenomedullin and urotensin-II, in human tumour cell lines of different origin: expression and effects on proliferation.Clin. Sci.2002103s2002 (S48)35S38S10.1042/CS103S035S12193050
     [Google Scholar]
  20. TakahashiK. TotsuneK. MurakamiO. AriharaZ. NoshiroT. HayashiY. ShibaharaS. Expression of urotensin II and its receptor in adrenal tumors and stimulation of proliferation of cultured tumor cells by urotensin II.Peptides200324230130610.1016/S0196‑9781(03)00039‑112668216
     [Google Scholar]
  21. ShenoudaA. DouglasS.A. OhlsteinE.H. GiaidA. Localization of urotensin-II immunoreactivity in normal human kidneys and renal carcinoma.J. Histochem. Cytochem.200250788588910.1177/00221554020500070212070267
     [Google Scholar]
  22. YeH. WangK. ZhaoJ. LuQ. WangM. SunB. ShenY. LiuH. PanéS. ChenX.Z. HeZ. SunJ. In situ sprayed nanovaccine suppressing exosomal PD-L1 by golgi apparatus disorganization for postsurgical melanoma immunotherapy.ACS Nano20231711106371065010.1021/acsnano.3c0173337213184
     [Google Scholar]
  23. MorimotoR. SatohF. MurakamiO. TotsuneK. AraiY. SuzukiT. SasanoH. ItoS. TakahashiK. Immunolocalization of urotensin II and its receptor in human adrenal tumors and attached non-neoplastic adrenal tissues.Peptides200829587388010.1016/j.peptides.2007.06.02517686550
     [Google Scholar]
  24. GiulianiL. LenziniL. AntonelloM. AldighieriE. BelloniA.S. FassinaA. Gomez-SanchezC. RossiG.P. Expression and functional role of urotensin-II and its receptor in the adrenal cortex and medulla: novel insights for the pathophysiology of primary aldosteronism.J. Clin. Endocrinol. Metab.200994268469010.1210/jc.2008‑113119001524
     [Google Scholar]
  25. ZengZ.P. LiuG.Q. LiH.Z. FanX.R. LiuD.M. TongL. ZhengX. LiuC. The effects of urotensin-II on proliferation of pheochromocytoma cells and mRNA expression of urotensin-II and its receptor in pheochromocytoma tissues.Ann. N. Y. Acad. Sci.20061073128428910.1196/annals.1353.03217102097
     [Google Scholar]
  26. De CobelliO. BuonerbaC. TerraccianoD. BotteroD. LucarelliG. BoveP. AltieriV. ComanI. PerdonàS. FacchiniG. BerrettaM. Di LorenzoG. GriecoP. NovellinoE. FrancoR. CaragliaM. ManiniC. MironeV. De PlacidoS. SonpavdeG. FerroM. Urotensin II receptor on preoperative biopsy is associated with upstaging and upgrading in prostate cancer.Future Oncol.201511223091309810.2217/fon.15.24926381851
     [Google Scholar]
  27. FrancoR. ZappavignaS. GigantinoV. LuceA. CantileM. CerroneM. FacchiniG. PerdonàS. PignataS. Di LorenzoG. ChieffiS. VitaleG. De SioM. SgambatoA. BottiG. YousifA.M. NovellinoE. GriecoP. CaragliaM. Urotensin II receptor determines prognosis of bladder cancer regulating cell motility/invasion.J. Exp. Clin. Cancer Res.20143314810.1186/1756‑9966‑33‑4824893613
     [Google Scholar]
  28. WuYQ. SongZ. ZhouCH. XingSH. PeiDS. ZhengJN. Expression of urotensin II and its receptor in human lung adenocarcinoma A549 cells and the effect of urotensin II on lung adenocarcinoma growth in vitro and in vivo.Oncol Rep.2010241179118410.3892/or_00000970220878108
     [Google Scholar]
  29. FedericoA. ZappavignaS. RomanoM. GriecoP. LuceA. MarraM. GravinaA.G. StiusoP. D’ArmientoF.P. VitaleG. TuccilloC. NovellinoE. LoguercioC. CaragliaM. Urotensin‐ II receptor is over‐expressed in colon cancer cell lines and in colon carcinoma in humans.Eur. J. Clin. Invest.201444328529410.1111/eci.1223124372535
     [Google Scholar]
  30. CamciC. KalenderM.E. SunerA. CengizB. OztuzcuS. BayraktarR. BorazanE. BabacanT. CamciC. The relationship between urotensin II and its receptor and the clinicopathological parameters of breast cancer.Med. Sci. Monit.2014201419142510.12659/MSM.89045925112588
     [Google Scholar]
  31. LiuD.G. ChenJ. WangH.X. LiB.X. Increased expression of urotensin II is associated with poor prognosis in hepatocellular carcinoma.Oncol. Lett.20161264961496810.3892/ol.2016.534428105202
     [Google Scholar]
  32. Le JoncourV. GuichetP.O. DembéléK.P. MutelA. CampisiD. PerzoN. DesruesL. ModzelewskiR. CouraudP.O. HonnoratJ. FerracciF.X. MarguetF. LaquerrièreA. VeraP. BohnP. LangloisO. MorinF. GandolfoP. CastelH. Targeting the urotensin ii/ut g protein-coupled receptor to counteract angiogenesis and mesenchymal hypoxia/necrosis in glioblastoma.Front. Cell Dev. Biol.2021965254410.3389/fcell.2021.65254433937253
     [Google Scholar]
  33. YuX.T. WangP.Y. ShiZ.M. DongK. FengP. WangH.X. WangX.J. Up-regulation of urotensin II and its receptor contributes to human hepatocellular carcinoma growth via activation of the PKC, ERK1/2, and p38 MAPK signaling pathways.Molecules20141912207682077910.3390/molecules19122076825514221
     [Google Scholar]
  34. LiY. ShiZ. YuX. FengP. WangX.J. The effects of urotensin II on migration and invasion are mediated by NADPH oxidase-derived reactive oxygen species through the c-Jun N-terminal kinase pathway in human hepatoma cells.Peptides20178810611410.1016/j.peptides.2016.12.00527988353
     [Google Scholar]
  35. ColyP.M. PerzoN. Le JoncourV. LecointreC. SchouftM.T. DesruesL. TononM.C. WurtzO. GandolfoP. CastelH. MorinF. Chemotactic G protein-coupled receptors control cell migration by repressing autophagosome biogenesis.Autophagy201612122344236210.1080/15548627.2016.123512527715446
     [Google Scholar]
  36. LecointreC. DesruesL. JoubertJ.E. PerzoN. GuichetP-O. Le JoncourV. BruléC. ChabbertM. LeducR. PrézeauL. LaquerrièreA. ProustF. GandolfoP. MorinF. CastelH. Signaling switch of the urotensin II vasosactive peptide GPCR: Prototypic chemotaxic mechanism in glioma.Oncogene201534395080509410.1038/onc.2014.43325597409
     [Google Scholar]
  37. HerrmannJ. Vascular toxic effects of cancer therapies.Nat. Rev. Cardiol.202017850352210.1038/s41569‑020‑0347‑232218531
     [Google Scholar]
  38. ClearyJ.F. AndersonB.M. EickhoffJ.C. KhuntiaD. FahlW.E. Significant suppression of radiation dermatitis in breast cancer patients using a topically applied adrenergic vasoconstrictor.Radiat. Oncol.201712120110.1186/s13014‑017‑0940‑729273054
     [Google Scholar]
  39. SorefC.M. FahlW.E. A new strategy to prevent chemotherapy and radiotherapy-induced alopecia using topically applied vasoconstrictor.Int. J. Cancer2015136119520310.1002/ijc.2896124811525
     [Google Scholar]
  40. GuoX. WangG. Advances in research on immune escape mechanism of glioma.CNS Neurosci. Ther.20232971709172010.1111/cns.1421737088950
     [Google Scholar]
  41. AndersenR.S. AnandA. HarwoodD.S.L. KristensenB.W. Tumor-associated microglia and macrophages in the glioblastoma microenvironment and their implications for therapy.Cancers20211317425510.3390/cancers1317425534503065
     [Google Scholar]
  42. LiM. XuH. QiY. PanZ. LiB. GaoZ. ZhaoR. XueH. LiG. Tumor-derived exosomes deliver the tumor suppressor miR-3591-3p to induce M2 macrophage polarization and promote glioma progression.Oncogene202241414618463210.1038/s41388‑022‑02457‑w36085418
     [Google Scholar]
  43. LinY.J. WeiK.C. ChenP.Y. LimM. HwangT.L. Roles of neutrophils in glioma and brain metastases.Front. Immunol.20211270138310.3389/fimmu.2021.70138334484197
     [Google Scholar]
  44. BasheerA.S. AbasF. OthmanI. NaiduR. Role of inflammatory mediators, macrophages, and neutrophils in glioma maintenance and progression: Mechanistic understanding and potential therapeutic applications.Cancers20211316422610.3390/cancers1316422634439380
     [Google Scholar]
  45. SrivastavaS. JacksonC. KimT. ChoiJ. LimM. A characterization of dendritic cells and their role in immunotherapy in glioblastoma: from preclinical studies to clinical trials.Cancers201911453710.3390/cancers1104053730991681
     [Google Scholar]
  46. HuJ.L. OmofoyeO.A. RudnickJ.D. KimS. TighiouartM. PhuphanichS. WangH. MazerM. GanawayT. ChuR.M. PatilC.G. BlackK.L. ShiaoS.L. WangR. YuJ.S. A phase I study of autologous dendritic cell vaccine pulsed with allogeneic stem-like cell line lysate in patients with newly diagnosed or recurrent glioblastoma.Clin. Cancer Res.202228468969610.1158/1078‑0432.CCR‑21‑286734862245
     [Google Scholar]
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Prognostic Significance and Functional Mechanism of UTS2 in Glioblastoma Multiforme
Curr. Cancer Drug Targets< 25, 636 (2025); https://doi.org/10.2174/0115680096275291231226081320
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  • Article Type:     Research Article
Keyword(s): cell proliferation; Glioblastoma multiform; immune activation; potent vasoconstrictor; survival analysis; vasoconstriction

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