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PXMP4 通过 PI3K/AKT 信号通路促进胃癌细胞上皮-间质转化。

PXMP4 promotes gastric cancer cell epithelial-mesenchymal transition via the PI3K/AKT signaling pathway.

机构信息

School of forensic Medicine, Xinxiang Medical University, Xinxiang, 453000, China.

Department of Pathology, Xinxiang Medical University, Xinxiang, 453000, China.

出版信息

Mol Biol Rep. 2024 Feb 24;51(1):350. doi: 10.1007/s11033-024-09312-z.

Abstract

BACKGROUND

Peroxisomal membrane protein 4 (PXMP4), a member of the peroxisome membrane protein PXMP2/4 family, participates in the progression of several malignant cancers. Nevertheless, the effect of PXMP4 in the development of gastric cancer (GC) is still unknown. As a result, the focus of this investigation was to elucidate the potential mechanisms of PXMP4 in GC.

METHODS AND RESULTS

Firstly, bioinformatics analysis results showed higher expression of PXMP4 in GC tissues. Secondly, clinical analysis of 57 patients with GC revealed correlations between PXMP4 expression and differentiation, depth of invasion, as well as TNM stage. Furthermore, individuals with elevated PXMP4 expression in GC exhibited an unfavorable prognosis. In vitro data showed the involvement of knockdown/overexpression of PXMP4 in the proliferation, invasion, and migration of GC cells, and triggering the epithelial-mesenchymal transition (EMT) of GC cells through the activation of the PI3K/AKT signaling pathway. LY294002, a PI3K/AKT inhibitor, inhibited the expression of PI3K/AKT-related proteins but did not affect the expression of PXMP4.

CONCLUSIONS

These findings indicate that PXMP4 potentially functions as an upstream molecule in the PI3K/AKT pathway, governing the EMT process in GC.

摘要

背景

过氧化物酶体膜蛋白 4(PXMP4)是过氧化物酶体膜蛋白 PXMP2/4 家族的一员,参与了几种恶性癌症的进展。然而,PXMP4 对胃癌(GC)发展的影响尚不清楚。因此,本研究的重点是阐明 PXMP4 在 GC 中的潜在作用机制。

方法和结果

首先,生物信息学分析结果显示 GC 组织中 PXMP4 的表达水平较高。其次,对 57 例 GC 患者的临床分析表明,PXMP4 表达与分化、浸润深度和 TNM 分期有关。此外,GC 中 PXMP4 表达升高的患者预后不良。体外数据显示,敲低/过表达 PXMP4 可影响 GC 细胞的增殖、侵袭和迁移,并通过激活 PI3K/AKT 信号通路触发 GC 细胞的上皮-间充质转化(EMT)。PI3K/AKT 抑制剂 LY294002 抑制了 PI3K/AKT 相关蛋白的表达,但不影响 PXMP4 的表达。

结论

这些发现表明,PXMP4 可能作为 PI3K/AKT 通路中的上游分子,调控 GC 中的 EMT 过程。

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