Exploring the oncogenic role of RGS19 in bladder cancer progression and prognosis

IF 2.3 4区生物学 Q4 CELL BIOLOGY

Acta histochemica Pub Date : 2024-10-31 DOI:10.1016/j.acthis.2024.152212

Lei Yan , Guangyue Luo , Chengxiang Han , Jialin Meng , Chaozhao Liang

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引用次数: 0

Abstract

This study investigates the role of autophagy-related genes (ARGs) in bladder cancer (BLCA), focusing on the regulator of G protein signaling 19 (RGS19). Using data from The Cancer Genome Atlas (TCGA) and the Human Autophagy Database (HADb), we identified RGS19 as significantly upregulated and linked to poor prognosis in BLCA. Kaplan-Meier survival analysis confirmed its association with increased mortality and. In vitro, RGS19 knockdown in BLCA cell lines inhibited proliferation, migration, and invasion, while inducing apoptosis and autophagy. Transmission electron microscopy showed autophagic structures in RGS19-silenced cells. In vivo, a xenograft mouse model demonstrated reduced tumor growth with RGS19 knockdown. Immunohistochemical (IHC) analysis revealed decreased Ki67 and increased autophagy markers in tumors with reduced RGS19. Pathway analysis suggested RGS19 acts through the cGMP-PKG signaling pathway, validated by altered expression of soluble guanylate cyclase (sGC), protein kinase G (PKG1), phosphodiesterase 5 A (PDE5A), vasodilator-stimulated phosphoprotein (VASP), and phosphorylated VASP (p-VASP) upon RGS19 knockdown. These results highlight RGS19 as a potential biomarker and therapeutic target in BLCA.

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探索 RGS19 在膀胱癌进展和预后中的致癌作用

本研究调查了自噬相关基因（ARGs）在膀胱癌（BLCA）中的作用，重点研究了G蛋白信号转导调节因子19（RGS19）。利用癌症基因组图谱（TCGA）和人类自噬数据库（HADb）的数据，我们发现RGS19在膀胱癌中显著上调并与不良预后相关。Kaplan-Meier生存分析证实了RGS19与死亡率增加和预后不良有关。在体外，敲除 BLCA 细胞系中的 RGS19 可抑制细胞增殖、迁移和侵袭，同时诱导细胞凋亡和自噬。透射电子显微镜显示了 RGS19 沉默细胞中的自噬结构。在体内，异种移植小鼠模型显示，RGS19 基因敲除可减少肿瘤生长。免疫组化（IHC）分析表明，在 RGS19 被敲除的肿瘤中，Ki67 降低，自噬标记物增加。通路分析表明，RGS19 是通过 cGMP-PKG 信号通路发挥作用的，可溶性鸟苷酸环化酶（sGC）、蛋白激酶 G（PKG1）、磷酸二酯酶 5 A（PDE5A）、血管扩张剂刺激的磷蛋白（VASP）和磷酸化 VASP（p-VASP）的表达在 RGS19 基因敲除后发生改变也验证了这一点。这些结果突出表明，RGS19 是 BLCA 的潜在生物标记物和治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Acta histochemica 生物-细胞生物学

CiteScore

4.60

自引率

4.00%

发文量

107

审稿时长

23 days

期刊介绍： Acta histochemica, a journal of structural biochemistry of cells and tissues, publishes original research articles, short communications, reviews, letters to the editor, meeting reports and abstracts of meetings. The aim of the journal is to provide a forum for the cytochemical and histochemical research community in the life sciences, including cell biology, biotechnology, neurobiology, immunobiology, pathology, pharmacology, botany, zoology and environmental and toxicological research. The journal focuses on new developments in cytochemistry and histochemistry and their applications. Manuscripts reporting on studies of living cells and tissues are particularly welcome. Understanding the complexity of cells and tissues, i.e. their biocomplexity and biodiversity, is a major goal of the journal and reports on this topic are especially encouraged. Original research articles, short communications and reviews that report on new developments in cytochemistry and histochemistry are welcomed, especially when molecular biology is combined with the use of advanced microscopical techniques including image analysis and cytometry. Letters to the editor should comment or interpret previously published articles in the journal to trigger scientific discussions. Meeting reports are considered to be very important publications in the journal because they are excellent opportunities to present state-of-the-art overviews of fields in research where the developments are fast and hard to follow. Authors of meeting reports should consult the editors before writing a report. The editorial policy of the editors and the editorial board is rapid publication. Once a manuscript is received by one of the editors, an editorial decision about acceptance, revision or rejection will be taken within a month. It is the aim of the publishers to have a manuscript published within three months after the manuscript has been accepted