RPS21 Enhances hepatocellular carcinoma development through GPX4 stabilization

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2024-11-14 DOI:10.1016/j.tranon.2024.102189

Siyuan Wu , Gaochao Wang , Likai Gu , Yinjie Zhang , Zhihuai Wang

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引用次数: 0

Abstract

The study highlights that RPS21, a gene encoding a component of the 40S ribosomal subunit, plays an oncogenic role in hepatocellular carcinoma (HCC) and may influence tumor aggressiveness by affecting antioxidant capacity. RPS21 was found to be upregulated in HCC through RNA-sequencing of clinical samples and analysis of the TCGA database. Kaplan-Meier survival analyses linked higher RPS21 expression to lower survival rates across multiple metrics (OS, PFS, RFS, DSS). Mutation analysis via the cBioPortal showed that primarily amplifications in RPS21 are associated with a poorer prognosis. Tissue microarrays confirmed higher RPS21 levels in tumor samples, which were associated with more advanced clinical stages and grades. Experimental interventions involving lentiviral knockdown or overexpression of RPS21 significantly altered HCC cell proliferation and migration. These findings were supported by mouse models, which showed impacts on tumor growth and metastasis. Further mechanistic studies indicated that RPS21 modulates the ubiquitination and stability of GPX4, a key player in ferroptosis and oxidative stress regulation in HCC cells. This comprehensive study, which merges bioinformatic analysis with laboratory research, positions RPS21 as a viable target for HCC therapy and opens new pathways for understanding and treating liver cancer.

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RPS21 通过稳定 GPX4 促进肝细胞癌的发展

该研究强调，RPS21是40S核糖体亚基的一个编码基因，它在肝细胞癌（HCC）中起着致癌作用，并可能通过影响抗氧化能力来影响肿瘤的侵袭性。通过对临床样本进行 RNA 测序和 TCGA 数据库分析，发现 RPS21 在 HCC 中上调。Kaplan-Meier生存分析将较高的RPS21表达与较低的多种指标（OS、PFS、RFS、DSS）生存率联系起来。通过 cBioPortal 进行的突变分析表明，RPS21 的主要扩增与较差的预后有关。组织微阵列证实，肿瘤样本中的RPS21水平较高，与较晚期的临床分期和分级有关。慢病毒敲除或过表达 RPS21 的实验干预能显著改变 HCC 细胞的增殖和迁移。这些发现得到了小鼠模型的支持，小鼠模型显示了对肿瘤生长和转移的影响。进一步的机理研究表明，RPS21 可调节 GPX4 的泛素化和稳定性，而 GPX4 是 HCC 细胞铁变态反应和氧化应激调节的关键角色。这项综合研究将生物信息学分析与实验室研究相结合，将 RPS21 定位为治疗 HCC 的可行靶点，为了解和治疗肝癌开辟了新途径。

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

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.