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Article Open Access

PLEKHA4 upregulation regulates KIRC cell proliferation through β‑catenin signaling

  • Authors:
    • Yuyang Yue
    • Guangqi An
    • Shuxia Cao
    • Xiangdan Li
    • Liping Du
    • Dongyuan Xu
    • Toufeng Jin
    • Lan Liu
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, Yanbian University Hospital, Yanji, Jilin 133000, P.R. China, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Key Laboratory of Cellular Function and Pharmacology of Jilin Province, Yanbian University, Yanji, Jilin 133002, P.R. China, Center of Morphological Experiment, Medical College of Yanbian University, Yanji, Jilin 133002, P.R. China, Department of General Surgery, Yanbian University Hospital, Yanji, Jilin 133000, P.R. China
    Copyright: © Yue et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 30
    |
    Published online on: November 13, 2024
       https://doi.org/10.3892/mmr.2024.13395
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Abstract

In the present study, pleckstrin homology domain‑containing family A member 4 (PLEKHA4) was identified as being upregulated in renal cell carcinoma, particularly within the kidney renal clear cell carcinoma (KIRC) subtype. The present study conducted bioinformatics analysis, Cell Counting Kit‑8 and cell migration assays, flow cytometry, western blotting and in vivo experiments with the aim of uncovering the role of PLEKHA4 in β‑catenin signaling in KIRC cells. Notably, PLEKHA4 upregulation was revealed to be associated with enhanced cell proliferation, indicating its potential role as an oncogene in KIRC. Mechanistically, knockdown of PLEKHA4 in KIRC cells led to decreased β‑catenin signaling and cyclin D1 expression and the induction of cell cycle arrest at the G1/S phase, suggesting that PLEKHA4 facilitated tumorigenesis through modulation of the Wnt/β‑catenin pathway. PLEKHA4 knockdown also inhibited cell viability, migration and colony formation, further emphasizing its role in cancer progression. Notably, overexpression of PLEKHA4 activated Wnt/β‑catenin signaling, reinforcing its role in promoting β‑catenin nuclear translocation and signaling activity. The present findings suggested that PLEKHA4 could serve as a potential therapeutic target for KIRC; inhibiting PLEKHA4 or modulating Wnt/β‑catenin signaling could provide new avenues for treatment strategies in KIRC.
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1 

Bahadoram S, Davoodi M, Hassanzadeh S, Bahadoram M, Barahman M and Mafakher L: Renal cell carcinoma: An overview of the epidemiology, diagnosis, and treatment. G Ital Nefrol. 39:2022–vol3. 2022.PubMed/NCBI

2 

Bex A, Albiges L, Ljungberg B, Bensalah K, Dabestani S, Giles RH, Hofmann F, Hora M, Kuczyk MA, Lam TB, et al: Updated European association of urology guidelines for cytoreductive nephrectomy in patients with synchronous metastatic clear-cell renal cell carcinoma. Eur Urol. 74:805–809. 2018. View Article : Google Scholar : PubMed/NCBI

3 

Botrugno OA, Fayard E, Annicotte JS, Haby C, Brennan T, Wendling O, Tanaka T, Kodama T, Thomas W, Auwerx J and Schoonjans K: Synergy between LRH-1 and beta-catenin induces G1 cyclin-mediated cell proliferation. Mol Cell. 15:499–509. 2004. View Article : Google Scholar : PubMed/NCBI

4 

Chow WH, Dong LM and Devesa SS: Epidemiology and risk factors for kidney cancer. Nat Rev Urol. 7:245–257. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Gobbo S, Eble JN, Grignon DJ, Martignoni G, MacLennan GT, Shah RB, Zhang S, Brunelli M and Cheng L: Clear cell papillary renal cell carcinoma: A distinct histopathologic and molecular genetic entity. Am J Surg Pathol. 32:1239–1245. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar : PubMed/NCBI

7 

Gao X, Liu Y, Hong S, Yang H, Guan B and Ma X: PLEKHA4 is associated with tumour microenvironment, stemness, proliferation and poor prognosis of gliomas. J Integr Neurosci. 22:1352023. View Article : Google Scholar : PubMed/NCBI

8 

Shami Shah A, Batrouni AG, Kim D, Punyala A, Cao W, Han C, Goldberg ML, Smolka MB and Baskin JM: PLEKHA4/kramer attenuates dishevelled ubiquitination to modulate Wnt and planar cell polarity signaling. Cell Rep. 27:2157–2170.e8. 2019. View Article : Google Scholar : PubMed/NCBI

9 

Tanton H, Sewastianik T, Seo HS, Remillard D, Pierre RS, Bala P, Aitymbayev D, Dennis P, Adler K, Geffken E, et al: A novel β-catenin/BCL9 complex inhibitor blocks oncogenic Wnt signaling and disrupts cholesterol homeostasis in colorectal cancer. Sci Adv. 8:eabm31082022. View Article : Google Scholar : PubMed/NCBI

10 

Nusse R and Clevers H: Wnt/β-catenin signaling, disease, and emerging therapeutic modalities. Cell. 169:985–999. 2017. View Article : Google Scholar : PubMed/NCBI

11 

Xu Q, Krause M, Samoylenko A and Vainio S: Wnt signaling in renal cell carcinoma. Cancers (Basel). 8:572016. View Article : Google Scholar : PubMed/NCBI

12 

Xu X, Zhang M, Xu F and Jiang S: Wnt signaling in breast cancer: Biological mechanisms, challenges and opportunities. Mol Cancer. 19:1652020. View Article : Google Scholar : PubMed/NCBI

13 

Li Y, Xiao X, Chen H, Chen Z, Hu K and Yin D: Transcription factor NFYA promotes G1/S cell cycle transition and cell proliferation by transactivating cyclin D1 and CDK4 in clear cell renal cell carcinoma. Am J Cancer Res. 10:2446–2463. 2020.PubMed/NCBI

14 

Ji J, Xu Y, Xie M, He X, Ren D, Qiu T, Liu W, Chen Z, Shi W, Zhang Z, et al: VHL-HIF-2α axis-induced SEMA6A upregulation stabilized β-catenin to drive clear cell renal cell carcinoma progression. Cell Death Dis. 14:832023. View Article : Google Scholar : PubMed/NCBI

15 

Jones J, Out H, Spentzos D, Kolia S, Inan M, Beecken WD, Fellbaum C, Gu X, Joseph M, Pantuck AJ, et al: Gene signatures of progression and metastasis in renal cell cancer. Clin Cancer Res. 11:5730–5739. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Wozniak MB, Le Calvez-Kelm F, Abedi-Ardekani B, Byrnes G, Durand G, Carreira C, Michelon J, Janout V, Holcatova I, Foretova L, et al: Integrative genome-wide gene expression profiling of clear cell renal cell carcinoma in Czech Republic and in the United States. PLoS One. 8:e578862013. View Article : Google Scholar : PubMed/NCBI

17 

MacDonald BT, Tamai K and He X: Wnt/beta-catenin signaling: Components, mechanisms, and diseases. Dev Cell. 17:9–26. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Maretzky T, Reiss K, Ludwig A, Buchholz J, Scholz F, Proksch E, de Strooper B, Hartmann D and Saftig P: ADAM10 mediates E-cadherin shedding and regulates epithelial cell-cell adhesion, migration, and beta-catenin translocation. Proc Natl Acad Sci USA. 102:9182–9187. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Shami Shah A, Cao X, White AC and Baskin JM: PLEKHA4 promotes Wnt/β-catenin signaling-mediated G1-S transition and proliferation in melanoma. Cancer Res. 81:2029–2043. 2021. View Article : Google Scholar : PubMed/NCBI

20 

Hedberg Y, Davoodi E, Roos G, Ljungberg B and Landberg G: Cyclin-D1 expression in human renal-cell carcinoma. Int J Cancer. 84:268–272. 1999. View Article : Google Scholar : PubMed/NCBI

21 

Albrecht LV, Tejeda-Muñoz N and De Robertis EM: Cell Biology of canonical Wnt signaling. Annu Rev Cell Dev Biol. 37:369–389. 2021. View Article : Google Scholar : PubMed/NCBI

22 

Niehrs C: The complex world of WNT receptor signalling. Nat Rev Mol Cell Biol. 13:767–779. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Bian J, Dannappel M, Wan C and Firestein R: Transcriptional regulation of Wnt/β-catenin pathway in colorectal cancer. Cells. 9:21252020. View Article : Google Scholar : PubMed/NCBI

24 

Hashemi M, Hasani S, Hajimazdarany S, Ghadyani F, Olyaee Y, Khodadadi M, Ziyarani MF, Dehghanpour A, Salehi H, Kakavand A, et al: Biological functions and molecular interactions of Wnt/β-catenin in breast cancer: Revisiting signaling networks. Int J Biol Macromol. 232:1233772023. View Article : Google Scholar : PubMed/NCBI

25 

Zhang Y and Wang X: Targeting the Wnt/β-catenin signaling pathway in cancer. J Hematol Oncol. 13:1652020. View Article : Google Scholar : PubMed/NCBI

26 

Krishnamurthy N and Kurzrock R: Targeting the Wnt/beta-catenin pathway in cancer: Update on effectors and inhibitors. Cancer Treat Rev. 62:50–60. 2018. View Article : Google Scholar : PubMed/NCBI

27 

Neiheisel A, Kaur M, Ma N, Havard P and Shenoy AK: Wnt pathway modulators in cancer therapeutics: An update on completed and ongoing clinical trials. Int J Cancer. 150:727–740. 2022. View Article : Google Scholar : PubMed/NCBI

28 

Zhang N, Wei P, Gong A, Chiu WT, Lee HT, Colman H, Huang H, Xue J, Liu M, Wang Y, et al: FoxM1 promotes β-catenin nuclear localization and controls Wnt target-gene expression and glioma tumorigenesis. Cancer Cell. 20:427–442. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Li P, Chen T, Kuang P, Liu F, Li Z, Liu F, Wang Y, Zhang W and Cai X: Aurora-A/FOXO3A/SKP2 axis promotes tumor progression in clear cell renal cell carcinoma and dual-targeting Aurora-A/SKP2 shows synthetic lethality. Cell Death Dis. 13:6062022. View Article : Google Scholar : PubMed/NCBI

30 

Swiatek M, Jancewicz I, Kluebsoongnoen J, Zub R, Maassen A, Kubala S, Udomkit A, Siedlecki JA, Sarnowski TJ and Sarnowska E: Various forms of HIF-1α protein characterize the clear cell renal cell carcinoma cell lines. IUBMB Life. 72:1220–1232. 2020. View Article : Google Scholar : PubMed/NCBI

31 

He W, Cong Z, Niu C, Cheng F, Yi T, Yao Z, Zhang Y, Jiang X, Sun X, Niu Z and Fu Q: A prognostic signature based on genes associated with m6A/m5C/m1A/m7G modifications and its immunological characteristics in clear cell renal cell carcinoma. Sci Rep. 14:187082024. View Article : Google Scholar : PubMed/NCBI

32 

Yin X, Wang J and Zhang J: Identification of biomarkers of chromophobe renal cell carcinoma by weighted gene co-expression network analysis. Cancer Cell Int. 18:2062018. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yue Y, An G, Cao S, Li X, Du L, Xu D, Jin T and Liu L: PLEKHA4 upregulation regulates KIRC cell proliferation through β‑catenin signaling. Mol Med Rep 31: 30, 2025.
APA
Yue, Y., An, G., Cao, S., Li, X., Du, L., Xu, D. ... Liu, L. (2025). PLEKHA4 upregulation regulates KIRC cell proliferation through β‑catenin signaling. Molecular Medicine Reports, 31, 30. https://doi.org/10.3892/mmr.2024.13395
MLA
Yue, Y., An, G., Cao, S., Li, X., Du, L., Xu, D., Jin, T., Liu, L."PLEKHA4 upregulation regulates KIRC cell proliferation through β‑catenin signaling". Molecular Medicine Reports 31.1 (2025): 30.
Chicago
Yue, Y., An, G., Cao, S., Li, X., Du, L., Xu, D., Jin, T., Liu, L."PLEKHA4 upregulation regulates KIRC cell proliferation through β‑catenin signaling". Molecular Medicine Reports 31, no. 1 (2025): 30. https://doi.org/10.3892/mmr.2024.13395
Copy and paste a formatted citation
x
Spandidos Publications style
Yue Y, An G, Cao S, Li X, Du L, Xu D, Jin T and Liu L: PLEKHA4 upregulation regulates KIRC cell proliferation through β‑catenin signaling. Mol Med Rep 31: 30, 2025.
APA
Yue, Y., An, G., Cao, S., Li, X., Du, L., Xu, D. ... Liu, L. (2025). PLEKHA4 upregulation regulates KIRC cell proliferation through β‑catenin signaling. Molecular Medicine Reports, 31, 30. https://doi.org/10.3892/mmr.2024.13395
MLA
Yue, Y., An, G., Cao, S., Li, X., Du, L., Xu, D., Jin, T., Liu, L."PLEKHA4 upregulation regulates KIRC cell proliferation through β‑catenin signaling". Molecular Medicine Reports 31.1 (2025): 30.
Chicago
Yue, Y., An, G., Cao, S., Li, X., Du, L., Xu, D., Jin, T., Liu, L."PLEKHA4 upregulation regulates KIRC cell proliferation through β‑catenin signaling". Molecular Medicine Reports 31, no. 1 (2025): 30. https://doi.org/10.3892/mmr.2024.13395
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