P2RX4通过钙介导的PI3K/AKT激活和免疫重塑促进肝细胞癌的进展。

IF 2.5 3区 医学 Q3 ONCOLOGY
Jianrong Wang, Yanmei Gu, Ze Niu, Futian Tang, Yumin Li
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引用次数: 0

摘要

背景:肝细胞癌(HCC)经常在晚期被发现。这限制了治疗选择并导致预后不良。P2RX4是atp门控离子通道,可调节钙内流。它参与细胞增殖、炎症过程和免疫反应。尽管如此,其在HCC中的作用仍然知之甚少。本研究探讨P2RX4在HCC中的表达、功能及免疫学作用。方法:采用TCGA-LIHC和TIMER2.0数据库检测P2RX4的表达。用免疫组织化学方法验证140个HCC组织的蛋白水平。利用P2RX4表达建立预后模型。P2RX4沉默后进行了体外研究。实验包括细胞增殖、入侵和集落形成。我们进一步进行了转录组测序。离子浓度用ICP-OES测定。Western blotting检测PI3K/AKT活化情况。结果:P2RX4在HCC组织中表达升高。其表达与肿瘤分期晚期及预后不良有关。P2RX4的沉默降低了肿瘤细胞的增殖和侵袭。它还能降低细胞内钙水平,抑制AKT磷酸化。P2RX4水平升高与M0巨噬细胞和treg增加、单核细胞数量减少以及对免疫治疗的预期反应较差相关。结论:P2RX4可能通过增加钙内流、激活PI3K/AKT通路和降低抗肿瘤免疫来促进HCC进展。它可能作为HCC的生物标志物和治疗靶点。此外,需要进行体内研究来验证这些发现。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
P2RX4 promotes hepatocellular carcinoma progression via calcium-mediated PI3K/AKT activation and immune remodeling.

Background: Hepatocellular carcinoma (HCC) is frequently identified at advanced stages. This constrains therapeutic options and results in poor prognosis. P2RX4 is an ATP-gated ion channel that modulates calcium influx. It participates in cellular proliferation, inflammatory processes, and immunological reactions. Nonetheless, its role in HCC remains poorly comprehended. This study explored the expression, function, and immunological effects of P2RX4 in HCC.

Methods: We examined P2RX4 expression using TCGA-LIHC and TIMER2.0 databases. Protein levels were validated using immunohistochemistry in 140 HCC tissues. A prognostic model was developed utilising P2RX4 expression. In vitro investigations were conducted subsequent to the silencing of P2RX4. The experiments encompassed cell proliferation, invasion, and colony formation. We further conducted transcriptome sequencing. Ion concentrations were quantified with ICP-OES. PI3K/AKT activation was evaluated using Western blotting.

Results: P2RX4 exhibited elevated expression in HCC tissues. Its expression was associated with advanced tumor stage and poor prognosis. Silencing of P2RX4 decreased tumour cell proliferation and invasion. It also reduced intracellular calcium levels and inhibited AKT phosphorylation. Elevated P2RX4 levels correlated with an increased presence of M0 macrophages and Tregs, a reduced number of monocytes, and a poorer anticipated response to immunotherapy.

Conclusions: P2RX4 may facilitate HCC progression by augmenting calcium influx, activating the PI3K/AKT pathway, and diminishing anti-tumor immunity. It may function as a biomarker and therapeutic target in HCC. Additional, in vivo investigations are required to validate these findings.

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来源期刊
CiteScore
4.70
自引率
15.60%
发文量
362
审稿时长
3 months
期刊介绍: World Journal of Surgical Oncology publishes articles related to surgical oncology and its allied subjects, such as epidemiology, cancer research, biomarkers, prevention, pathology, radiology, cancer treatment, clinical trials, multimodality treatment and molecular biology. Emphasis is placed on original research articles. The journal also publishes significant clinical case reports, as well as balanced and timely reviews on selected topics. Oncology is a multidisciplinary super-speciality of which surgical oncology forms an integral component, especially with solid tumors. Surgical oncologists around the world are involved in research extending from detecting the mechanisms underlying the causation of cancer, to its treatment and prevention. The role of a surgical oncologist extends across the whole continuum of care. With continued developments in diagnosis and treatment, the role of a surgical oncologist is ever-changing. Hence, World Journal of Surgical Oncology aims to keep readers abreast with latest developments that will ultimately influence the work of surgical oncologists.
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