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蛋白细胞分裂调控因子 1(PRC1)上调促进肝癌免疫抑制。

Protein Regulator of Cytokinesis 1 (PRC1) Upregulation Promotes Immune Suppression in Liver Hepatocellular Carcinoma.

机构信息

Institutes of Biomedical Sciences, And Key Laboratory of Medical Molecular Virology of Ministry of Education & Ministry of Health, School of Basic Medical Sciences, Fudan University, 200032 Shanghai, China.

Laboratory of Medical Molecular Biology, Experimental Teaching Center, School of Basic Medical Sciences, Fudan University, 200032 Shanghai, China.

出版信息

J Immunol Res. 2022 Aug 9;2022:7073472. doi: 10.1155/2022/7073472. eCollection 2022.

Abstract

Liver hepatocellular carcinoma (LIHC) is a malignant cancer with widespread prevalence. The suppressive immune environment causes largely refractory to current treatment. The protein regulator of cytokinesis 1 (PRC1) is an essential gene for cytokinesis and is involved in cancer pathogenesis. However, the functions of PRC1 have been barely clarified, especially in LIHC. Here, we investigated the expression, prognostic value, and functions of PRC1 in LIHC. Pan-cancer analysis revealed the overexpression of PRC1 in the Cancer Genome Atlas (TCGA) database. Four LIHC datasets from the Gene Expression Omnibus (GEO) database confirmed the PRC1 overexpression in LIHC. The mRNA and protein levels of PRC1 in LIHC cells were higher than in normal liver cells. The overexpression of PRC1 predicted progressed clinical stage and poor prognosis of LIHC. We further investigated the functions of PRC1 by performing the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and Gene Set Enrichment Analysis (GSEA) of its coexpressing genes. High PRC1 expression was associated with increased genome instability of LIHC. Moreover, PRC1 was positively correlated with the infiltration of suppressive immune cells like T regulatory cells (Tregs) and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and was negatively correlated with the effector immune cells' infiltration, including B cells and CD8+ T cells. In addition, PRC1 was positively correlated with the expression of tumor immune checkpoint molecules. Taken together, PRC1 overexpression contributes to the genome instability and the suppressive immune microenvironment of LIHC. Thus, PRC1 has the potential to be a prognostic marker and therapeutic target of LIHC.

摘要

肝细胞肝癌(LIHC)是一种广泛流行的恶性肿瘤。抑制性免疫环境导致其对当前治疗方法产生很大的耐药性。细胞分裂蛋白调控因子 1(PRC1)是细胞分裂所必需的基因,参与癌症的发病机制。然而,PRC1 的功能尚未得到充分阐明,特别是在 LIHC 中。在这里,我们研究了 PRC1 在 LIHC 中的表达、预后价值和功能。泛癌症分析显示,PRC1 在癌症基因组图谱(TCGA)数据库中过表达。来自基因表达综合数据库(GEO)的四个 LIHC 数据集证实了 LIHC 中 PRC1 的过表达。LIHC 细胞中 PRC1 的 mRNA 和蛋白水平均高于正常肝细胞。PRC1 的过表达预示着 LIHC 临床分期进展和预后不良。我们通过对其共表达基因进行基因本体论(GO)、京都基因与基因组百科全书(KEGG)分析和基因集富集分析(GSEA)进一步研究了 PRC1 的功能。高 PRC1 表达与 LIHC 的基因组不稳定性增加有关。此外,PRC1 与抑制性免疫细胞如调节性 T 细胞(Tregs)和多形核髓系来源的抑制细胞(PMN-MDSCs)的浸润呈正相关,与效应性免疫细胞的浸润呈负相关,包括 B 细胞和 CD8+T 细胞。此外,PRC1 与肿瘤免疫检查点分子的表达呈正相关。总之,PRC1 的过表达有助于 LIHC 的基因组不稳定性和抑制性免疫微环境。因此,PRC1 有可能成为 LIHC 的预后标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ab1/9381293/8d3abf2fa18a/JIR2022-7073472.001.jpg

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