HRAS 通过上调肝细胞癌中的 HSPB1 诱导铁变态反应

IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS
Wei Chen, Xiang Zhang, Bin Zhang, Minhui Chi, Qi Zheng
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引用次数: 0

摘要

研究背景本研究旨在探讨 HRAS 和 HSPB1 在铁变态反应中的作用机制。原发性肝癌是全球肿瘤死亡的第三大原因。肝细胞癌(HCC)占原发性肝癌病例的75%-85%。HRAS 和 HSPB1 在多种细胞中共同表达,并参与肿瘤进展调控。然而,它们在 HCC 中的表达调控和作用尚未见报道:方法:我们在体外实验中研究了 HRAS 和 HSPB1 对铁变态反应的影响。方法:我们在体外实验中研究了HRAS和HSPB1对铁变态反应的影响,并通过在HCC细胞中转染特异性siRNA或过表达质粒研究了HRAS和HSPB1对铁变态反应的作用和机制:结果:生物信息学分析表明,HRAS和HSPB1在HCC组织中高表达,与HCC患者的不良预后有关。在体外,HRAS 的过表达降低了 HCC 细胞内铁、ROS 和 MDA 的生成水平。从机理上讲,HRAS增加了GPX4的表达,降低了ACSL4和P53的水平。HRAS 还增加了 HSPB1 的表达,而 HRAS 敲除会降低 HCC 细胞中 HSPB1 的水平。重要的是,HSPB1的过表达逆转了HRAS增加的铁、MDA和ROS浓度,并消除了HRAS诱导的铁变态反应。此外,HRAS通过靶向HSPB1增强了肿瘤的增殖和侵袭:结论:HRAS对HSPB1的调控增强了HCC细胞对铁变态反应的抵抗力。HRAS通过上调HSPB1促进增殖和侵袭。这项研究为治疗 HCC 提供了一种新的潜在策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
HRAS Induces Ferroptosis through Upregulating HSPB1 in Hepatocellular Carcinoma.

Background: The aim of this study is to explore the mechanism of HRAS and HSPB1 in ferroptosis. Primary liver cancer is the third leading cause of tumor death worldwide. Hepatocellular carcinoma (HCC) constitutes 75%-85% of cases of primary liver cancer. HRAS and HSPB1 co-express in multiple cells and participate in tumor progression regulation. However, their expression regulation and role in HCC have not been reported.

Methods: We investigated the effects of HRAS and HSPB1 on ferroptosis in in vitro experiments. Here, the role and mechanism of HRAS and HSPB1 on ferroptosis were investigated by transfecting the specific siRNA or overexpressing plasmids in HCC cells.

Results: Bioinformatics analysis proved that HRAS and HSPB1 were highly expressed in HCC tissues and associated with poor prognosis of patients with HCC. In vitro, HRAS overexpression reduced the level of intracellular iron, ROS, and MDA production in HCC cells. Mechanistically, HRAS increased GPX4 expression and decreased the levels of ACSL4 and P53. HRAS also increased HSPB1 expression, and HRAS knockdown downregulated HSPB1 levels in HCC cells. Importantly, overexpression of HSPB1 reversed HRAS-increased concentration of iron, MDA, and ROS and eliminated HRAS-induced ferroptosis. Moreover, HRAS enhanced the proliferation and invasion by targeting HSPB1.

Conclusion: The regulation of HSPB1 by HRAS enhanced the resistance of HCC cells to ferroptosis. HRAS promoted proliferation and invasion by upregulating HSPB1. This research provides a new potential strategy for HCC treatment.

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来源期刊
CiteScore
3.10
自引率
5.60%
发文量
327
审稿时长
7.5 months
期刊介绍: Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal: Target identification and validation Assay design, development, miniaturization and comparison High throughput/high content/in silico screening and associated technologies Label-free detection technologies and applications Stem cell technologies Biomarkers ADMET/PK/PD methodologies and screening Probe discovery and development, hit to lead optimization Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) Chemical library design and chemical diversity Chemo/bio-informatics, data mining Compound management Pharmacognosy Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products) Natural Product Analytical Studies Bipharmaceutical studies of Natural products Drug repurposing Data management and statistical analysis Laboratory automation, robotics, microfluidics, signal detection technologies Current & Future Institutional Research Profile Technology transfer, legal and licensing issues Patents.
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