PLAUR facilitates the progression of clear cell renal cell carcinoma by activating the PI3K/AKT/mTOR signaling pathway.

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  • Additional Information
    • Source:
      Publisher: PeerJ Inc Country of Publication: United States NLM ID: 101603425 Publication Model: eCollection Cited Medium: Internet ISSN: 2167-8359 (Electronic) Linking ISSN: 21678359 NLM ISO Abbreviation: PeerJ Subsets: MEDLINE
    • Publication Information:
      Original Publication: Corte Madera, CA : PeerJ Inc.
    • Subject Terms:
      Carcinoma, Renal Cell*/pathology ; Carcinoma, Renal Cell*/genetics ; Carcinoma, Renal Cell*/metabolism ; TOR Serine-Threonine Kinases*/metabolism ; TOR Serine-Threonine Kinases*/genetics ; Kidney Neoplasms*/pathology ; Kidney Neoplasms*/genetics ; Kidney Neoplasms*/metabolism ; Signal Transduction* ; Proto-Oncogene Proteins c-akt*/metabolism ; Proto-Oncogene Proteins c-akt*/genetics ; Phosphatidylinositol 3-Kinases*/metabolism ; Phosphatidylinositol 3-Kinases*/genetics ; Disease Progression* ; Cell Proliferation*/genetics; Humans ; Cell Line, Tumor ; Male ; Female ; Apoptosis ; Cell Movement/genetics ; Middle Aged ; Gene Expression Regulation, Neoplastic ; Prognosis ; Up-Regulation
    • Abstract:
      Background: PLAUR has been found upregulated in various tumors and closely correlated with the malignant phenotype of tumor cells. The aim of this study was to investigate the relationship between PLAUR and clear cell renal cell carcinoma (ccRCC) and its potential mechanism of promoting tumor progression.
      Methods: The expression levels and clinical significance of PLAUR, along with the associated signaling pathways, were extensively investigated in ccRCC samples obtained from The Cancer Genome Atlas (TCGA). PLAUR expression in 20 pairs of ccRCC tumor tissues and the adjacent tissues was assessed using qRT-PCR and IHC staining. Additionally, a series of in vitro experiments were conducted to investigate the impact of PLAUR suppression on cellular proliferation, migration, invasion, cell cycle progression, and apoptosis in ccRCC. The Western blot analysis was employed to investigate the expression levels of pivotal genes associated with the PI3K/AKT/mTOR signaling pathway.
      Results: The expression of PLAUR was significantly upregulated in ccRCC compared to normal renal tissues, and higher PLAUR expression in ccRCC was associated with a poorer prognosis than low expression. The in-vitro functional investigations demonstrated that knockdown of PLAUR significantly attenuated the proliferation, migration, and invasion capabilities of ccRCC cells. Concurrently, PLAUR knockdown effectively induced cellular apoptosis, modulated the cell cycle, inhibited the EMT process, and attenuated the activation of the PI3K/AKT/mTOR signaling pathway. PLAUR may represent a key mechanism underlying ccRCC progression.
      Conclusions: The involvement of PLAUR in ccRCC progression may be achieved through the activation of the PI3K/AKT/mTOR signaling pathway, making it a reliable biomarker for the identification and prediction of ccRCC.
      Competing Interests: The authors declare there are no competing interests.
      (©2024 Qin et al.)
    • References:
      Drug News Perspect. 2008 Mar;21(2):107-16. (PMID: 18389102)
      CA Cancer J Clin. 2017 Nov;67(6):507-524. (PMID: 28961310)
      J Biomol Struct Dyn. 2024 Jan 3;:1-18. (PMID: 38173169)
      Cancers (Basel). 2022 Jan 04;14(1):. (PMID: 35008402)
      Mol Cell Biol. 2020 Jan 16;40(3):. (PMID: 31767633)
      PLoS One. 2022 Jun 8;17(6):e0269595. (PMID: 35675366)
      Appl Microbiol Biotechnol. 2020 Jan;104(2):575-587. (PMID: 31832711)
      J Inflamm Res. 2021 Sep 15;14:4629-4641. (PMID: 34552345)
      Front Oncol. 2020 Jan 24;10:3. (PMID: 32038982)
      Proteomics. 2019 Nov;19(21-22):e1900026. (PMID: 31402590)
      Int J Biol Sci. 2022 Jul 11;18(11):4560-4577. (PMID: 35864968)
      Onco Targets Ther. 2019 Jan 30;12:953-958. (PMID: 30774381)
      Nat Commun. 2020 Feb 17;11(1):929. (PMID: 32066735)
      Am J Kidney Dis. 2023 Dec;82(6):743-761. (PMID: 37855786)
      Anticancer Drugs. 2001 Jun;12(5):387-400. (PMID: 11395568)
      Recent Pat Anticancer Drug Discov. 2008 Jan;3(1):1-13. (PMID: 18289119)
      Int J Mol Sci. 2023 Aug 24;24(17):. (PMID: 37685983)
      Int J Mol Sci. 2022 May 09;23(9):. (PMID: 35563651)
      J Cancer. 2020 Jun 21;11(17):4996-5006. (PMID: 32742447)
      Anticancer Drugs. 2006 Nov;17(10):1109-17. (PMID: 17075310)
      Biomaterials. 2018 Mar;157:62-75. (PMID: 29245052)
      Oncologist. 2021 Aug;26(8):e1460-e1469. (PMID: 33687124)
      Int J Mol Sci. 2021 Apr 22;22(9):. (PMID: 33921923)
      Nat Rev Nephrol. 2020 Mar;16(3):156-172. (PMID: 31636445)
      Clin Genitourin Cancer. 2017 Dec;15(6):717-723. (PMID: 28552571)
      Am J Transl Res. 2019 Oct 15;11(10):6475-6486. (PMID: 31737199)
      Int J Mol Sci. 2023 May 07;24(9):. (PMID: 37176098)
      Acta Pharm Sin B. 2015 Sep;5(5):378-89. (PMID: 26579469)
      J Cell Physiol. 2020 Sep;235(9):6268-6286. (PMID: 31990070)
      Crit Rev Eukaryot Gene Expr. 2023;33(7):65-80. (PMID: 37602454)
      World J Urol. 2020 Oct;38(10):2501-2511. (PMID: 31797075)
      Genes (Basel). 2022 Nov 07;13(11):. (PMID: 36360294)
      Am J Hum Genet. 1992 Mar;50(3):492-7. (PMID: 1311495)
      Eur J Med Chem. 2016 Feb 15;109:314-41. (PMID: 26807863)
      Mol Cancer. 2023 Aug 18;22(1):138. (PMID: 37596643)
      Front Oncol. 2022 Aug 16;12:834524. (PMID: 36052236)
      Int J Biochem Cell Biol. 2009 Aug-Sep;41(8-9):1731-8. (PMID: 19433314)
      J Cancer. 2020 Jan 1;11(1):16-24. (PMID: 31892969)
      Sci Rep. 2023 Nov 2;13(1):18922. (PMID: 37919459)
      Nat Rev Clin Oncol. 2023 Jun;20(6):353. (PMID: 37041275)
      FASEB J. 2022 Jun;36(6):e22368. (PMID: 35596683)
      CA Cancer J Clin. 2023 Jan;73(1):17-48. (PMID: 36633525)
      Cancer Discov. 2018 Jul;8(7):850-865. (PMID: 29875134)
      Cell Physiol Biochem. 2018;47(5):1909-1924. (PMID: 29961070)
      Cancer Treat Rev. 2007 Oct;33(6):521-7. (PMID: 17658220)
      Funct Integr Genomics. 2023 Aug 8;23(3):269. (PMID: 37552345)
    • Contributed Indexing:
      Keywords: Apoptosis; Cell cycle; Clear cell renal cell carcinoma; EMT; PI3K/AKT/mTOR; PLAUR
    • Molecular Sequence:
      figshare 10.6084/m9.figshare.25271203.v4
    • Accession Number:
      EC 2.7.11.1 (TOR Serine-Threonine Kinases)
      EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
      EC 2.7.1.1 (MTOR protein, human)
      EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
    • Publication Date:
      Date Created: 20240701 Date Completed: 20240701 Latest Revision: 20240702
    • Publication Date:
      20240702
    • Accession Number:
      PMC11214736
    • Accession Number:
      10.7717/peerj.17555
    • Accession Number:
      38948215