Construction of Novel lncRNA-miRNA-mRNA Network Associated With Recurrence and Identification of Immune-Related Potential Regulatory Axis in Hepatocellular Carcinoma.
Construction of Novel lncRNA-miRNA-mRNA Network Associated With Recurrence and Identification of Immune-Related Potential Regulatory Axis in Hepatocellular Carcinoma.
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肝细胞癌复发相关新型lncRNA-miRNA-mRNA网络的构建及免疫相关潜在调节轴的鉴定
DOI：
10.3389/fonc.2021.626663
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发表时间：
2021
影响因子：
4.7
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Zhan T;Gao X;Wang G;Li F;Shen J;Lu C;Xu L;Li Y;Zhang J
肝细胞癌（HCC）是全球最常见的恶性肿瘤之一。尽管治疗方法不断改进，但术后高复发率仍然是一个亟待解决的问题。为了确定肝癌复发的潜在机制并识别预后基因，整合并分析了来自基因表达综合库（GEO）和癌症基因组图谱（TCGA）的数据。对肝癌组织和正常肝组织中的差异表达基因进行鉴定，并构建蛋白质相互作用网络寻找枢纽基因。使用R语言和GEPIA进行临床相关性分析和无病生存（DFS）分析，以确定复发相关基因。相关性分析被用来确定一个潜在的调节轴。采用双荧光素酶报告基因分析法证实长非编码RNA（lncRNA）-microRNA（miRNA）-mRNA调控轴的可靠性。使用TIMER数据库进行免疫浸润分析。采用实时定量聚合酶链反应（RT-qPCR）验证免疫基因标记与ASF 1B之间的相关性。在这项工作中，我们发现9个lncRNA和5个mRNA在复发患者的HCC组织中显著过表达。SNHG 3、LINC 00205、ASF 1B、AURKB、CCNB 1、CDKN 3、DTL与HCC分级、分期密切相关。生存分析显示，这7个DEG与DFS差显著相关。相关性分析表明SNHG 3-miR-214- 3 p-ASF 1B是一个潜在的调控轴。双荧光素酶报告基因检测显示SNHG 3和ASF 1B与miR-214- 3 p直接结合。ASF 1B受miRNA-214- 3 p负调控，SNHG 3过表达可抑制miRNA-214- 3 p的表达。此外，ASF 1B与免疫浸润呈正相关。降低ASF 1B表达可明显抑制肝癌细胞中CD 86、CD 8、STAT 1、STAT 4、CD 68和PD 1的表达。流式细胞术显示SNHG 3通过调节ASF 1B促进PD-1的表达。同时，在B细胞、CD 8 + T细胞或中性粒细胞减少以及CD 4 + T细胞富集的亚组中，升高的ASF 1 B预测HCC患者预后不良。总之，我们发现新的lncRNA SNHG 3/miR-214- 3 p/ASF 1B轴可以通过调节免疫浸润促进HCC的复发。
Hepatocellular carcinoma (HCC) is one of the most common malignant diseases globally. Despite continuous improvement of treatment methods, high postoperative recurrence rate remains an urgent problem. In order to determine the mechanism underlying recurrence of liver cancer and identify prognostic genes, data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were integrated and analyzed. Differentially expressed genes (DEGs) between HCC tissue and normal liver tissue were identified, and a protein–protein interaction network was constructed to find hub genes. Clinical correlation analysis and disease-free survival (DFS) analysis were performed using the R language and GEPIA to identify relapse-related genes. Correlation analysis was used to identify a potential regulatory axis. Dual-luciferase reporter gene assay was used to confirm the reliability of the long non-coding RNA (lncRNA)–microRNA (miRNA)–mRNA regulatory axis. Immune infiltration analysis was performed using the TIMER database. Correlations between immune gene markers and ASF1B were verified using quantitative real-time polymerase chain reaction (RT-qPCR). In this work, we found that nine lncRNAs and five mRNAs were significantly overexpressed in HCC tissues from patients with recurrence. SNHG3, LINC00205, ASF1B, AURKB, CCNB1, CDKN3, and DTL were also closely related to HCC grade and stage. Survival analysis showed that these seven DEGs were significantly correlated with poor DFS. Correlation analysis identified SNHG3–miR-214-3p–ASF1B as a potential regulatory axis. Dual-luciferase reporter gene assay showed that SNHG3 and ASF1B directly bound to miR-214-3p. ASF1B was negatively regulated by miRNA-214-3p, and overexpression of SNHG3 could inhibit the expression of miRNA-214-3p. In addition, ASF1B was positively correlated with immune infiltration. A reduction in ASF1B could markedly inhibit the expression of CD86, CD8, STAT1, STAT4, CD68, and PD1 in HCC cells. Flow cytometry showed that SNHG3 promoted the PD-1 expression by regulating ASF1B. Meanwhile, elevated ASF1B predicted poor prognosis of HCC patients in subgroups with decreased B cells, CD8+ T cells, or neutrophils, and those with enriched CD4+ T cells. In conclusion, we found that a novel lncRNA SNHG3/miR-214-3p/ASF1B axis could promote the recurrence of HCC by regulating immune infiltration.
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影响因子：
3.8
作者：
Lu, Jun;Xu, Yu;Huang, Chang-ming
通讯作者：
Huang, Chang-ming
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作者：
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作者：
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影响因子：
10.1
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影响因子：
5.8
作者：
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