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ISSN 0028-2685
ISSN 1338-4317 (online)

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neo_2026_251230N536

Title: RNA-binding protein hnRNPD promotes the proliferation of Wilms’ tumor cells through activating the p38 MAPK signaling pathway
Author: Chunlei Yang, Man Liao, Haibin Bao, Haolun Xu, Jun Wang, Man Zhang, Can Li, Tian Zheng, Gang Li

Abstract: Wilms’ tumor (WT) represents a kidney carcinoma predominantly affecting children aged five years and younger. Heterogeneous nuclear ribonucleoprotein D (hnRNPD), an RNA-binding protein, has been implicated in oncogenic processes across various tumor types, whereas its expression pattern and biological function in WT remain largely unknown. hnRNPD expression within WT tissues was evaluated using publicly available databases, and co-expressed genes were identified through bioinformatic analysis. In vitro, hnRNPD expression in WT cell lines 17.94 and HFWT was modulated via gene silencing or overexpression. We subsequently carried out functional assays to assess cell proliferation and apoptosis. Molecular experiments were conducted to determine p38 mitogen-activated protein kinase (p38 MAPK) pathway activation status within cells with altered hnRNPD expression. Furthermore, SB203580 was utilized to pharmacologically inhibit this pathway to investigate the mechanism of hnRNPD in regulating WT cell proliferation. Data showed that hnRNPD was upregulated in WT tissues and cells. Silencing hnRNPD significantly inhibited WT cell proliferation and promoted apoptosis. Conversely, overexpression of hnRNPD produced the opposing effects. MAPK14, the gene encoding the p38α isoform of p38 MAPK, was identified as a core gene within the hnRNPD co-expression network. Furthermore, the phosphorylation level of p38 MAPK in WT cells was markedly elevated compared to that in normal cells. However, inhibition of the p38 MAPK pathway using SB203580 suppressed WT cell proliferation. Notably, SB203580 effectively counteracted the pro-proliferative effect of hnRNPD overexpression on malignant WT cell growth. In conclusion, hnRNPD is highly expressed in WT and plays a significant role in promoting the malignant proliferation of WT cells. The underlying molecular mechanism involves the regulation of p38 MAPK signaling pathway activation.

Keywords: Wilms’ tumor; heterogeneous nuclear ribonucleoprotein D; cell proliferation; p38 mitogen-activated protein kinase
Year: , Volume: , Issue: Page From: , Page To:
doi:10.4149/neo_2026_251230N536


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