研究动态
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对EZH2的分析:肝细胞癌相关CeRNA的机制鉴定及其免疫测定研究。

Analysis on EZH2: mechanism identification of related CeRNA and its immunoassay in hepatocellular carcinoma.

发表日期:2023 Aug 25
作者: Haoran Zhao, Haishi Liu, Wenli Kang, Chao Zhan, Yingchun Man, Tong Qu
来源: Cellular & Molecular Immunology

摘要:

为了筛选与增强子of zeste homolog 2(EZH2)相关的潜在信号通路,基于ceRNA机制,并分析E2H2与各种免疫细胞浸润深度之间的相关性。还分析了不同免疫检查点之间的关系。首先,使用TCGA数据库分析了18种恶性肿瘤的pan-cancer(总体癌)中EZH2的表达。对374例肝细胞癌(HCC)组织和50例正常组织进行了差异表达、总生存(OS)和无进展生存(PFS)的分析。然后,我们对目标基因进行了GO和KEGG富集分析。还利用starbase数据库分析了mRNA-miRNA和miRNA-long non-coding RNA(lncRNA)之间的相关性,以确定与EZH2相关的潜在ceRNA机制。最后,进行了EZH2的免疫测定和药物敏感性分析。 筛选出了七条潜在的与EZH2相关的ceRNA通路,即lncRNA: Small Nucleolar RNA Host Gene 1(SNHG1),SNHG 3和SNHG 6-miR-101-3p-EZH2;以及lncRNA: Long Intergenic Non-Protein Coding RNA 1978(LINC01978),SNHG12,Ring Finger Protein 216 Pseudogene 1(RNF216P1)和Coiled-coil Domain Containing 18 Antisense RNA 1(CCDC18-AS1)-let-7c-5p-EZH2。最后,通过qPCR鉴定了4个与EZH2相关的潜在ceRNA通路。 根据免疫相关性分析,EZH2可能与T细胞协助滤泡状、T细胞簇集分化(CD)4记忆激活、巨噬细胞M0和B细胞记忆呈正相关(P < 0.05,cof > 0.2);而与T细胞CD4+记忆静息呈负相关(P < 0.05,cof < -0.2)。并且EZH2与细胞程序性死亡1(PDCD1)(R = 0.22)、CD274(R = 0.3)和细胞毒性T淋巴细胞相关蛋白4(CTLA4)(R = 0.23)呈正相关。根据药物敏感性分析,高表达组患者对Sorafenib、5-Fluorouracil、Doxorubicin、Etoposide、Paclitaxel和Vinorelbine等各种药物的作用更敏感。 本研究揭示了增强子of zeste homolog 2(EZH2)相关的七条ceRNA机制潜在通路:lncRNA(SNHG3、6)-Mir-101-3P-EZH2;lncRNA(SNHG12、RNF216P1)-let-7c-5p-EZH2。我们还分析了EZH2的免疫和药物敏感性。我们的研究证明,EZH2在HCC中仍然具有巨大的研究前景。© 2023. BioMed Central Ltd.,Springer Nature的一部分。
To screen the possible potential signaling pathways related to enhancer of zeste homolog 2 (EZH2) based on ceRNA mechanism, and to analyze the correlation between E2H2 and depths of various immune cell infiltration depths. The relationship between different immune checkpoints were also analyzed.First, the expression of EZH2 in pan-cancer (18 malignancies) was analyzed with the TCGA database. Hepatocellular carcinoma (HCC) tissues of 374 cases and normal tissues of 50 cases were analyzed in terms of the differential expression, overall survival (OS) and progression-free-survival (PFS). Then, we conducted GO and KEGG enrichment analysis on target gene. We also analyzed mRNA-miRNA and MicroRNA (miRNA)- long non-coding RNA (lncRNA) correlation with starbase databse, so as to determine the potential ceRNA mechanism associated with EZH2. Finally, immunoassay and drug-sensitivity analysis of EZH2 was performed.Seven potential EZH2-related ceRNA pathways were screened out, namely lncRNA: Small Nucleolar RNA Host Gene 1 (SNHG1), SNHG 3, and SNHG 6-miR-101-3p-EZH2; and lncRNA: Long Intergenic Non-Protein Coding RNA 1978 (LINC01978), SNHG12, Ring Finger Protein 216 Pseudogene 1 (RNF216P1), and Coiled-coil Domain Containing 18 Antisense RNA 1 (CCDC18-AS1)-let-7c-5p-EZH2. Finally, 4 potential EZH2-related ceRNA pathways were identified through qPCR.According to immune correlation analysis, EZH2 may be positively correlated with T cells follicular helper, T cells Cluster of differentiation (CD)4 memory activated, Macrophages M0, and B cells memory (P < 0.05, cof > 0.2); while be negatively correlated with T cells CD4 + memory resting (P < 0.05, cof < -0.2). And EZH2 is positively correlated with Programmed Cell Death 1 (PDCD1) (R = 0.22), CD274 (R = 0.3) and Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA4) (R = 0.23). According to drug sensitivity analysis, patients in the high expression group were more susceptible to the effects of various drugs including Sorafenib, 5-Fluorouracil, Doxorubicin, Etoposide, Paclitaxel, and Vinorelbine than those with low expression.This study revealed seven potential pathways of Enhancer of Zeste Homolog 2 (EZH2)-related ceRNA mechanisms: lncRNA (SNHG3, 6) -Mir-101-3P-ezh2; lncRNA (SNHG12, RNF216P1)-let-7c-5p-EZH2. We also analyzed the immunity and drug sensitivity of EZH2. Our study proves that EZH2 still has great research prospects in HCC.© 2023. BioMed Central Ltd., part of Springer Nature.