PLEKHA4 upregulation regulates KIRC cell proliferation through &beta;‑catenin signaling

Yue,Yuyang; An,Guangqi; Cao,Shuxia; Li,Xiangdan; Du,Liping; Xu,Dongyuan; Jin,Toufeng; Liu,Lan

doi:10.3892/mmr.2024.13395

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
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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
Published online on: November 13, 2024 https://doi.org/10.3892/mmr.2024.13395
Article Number: 30
Copyright: © Yue et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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