Centromere protein E as a novel biomarker and potential therapeutic target for retinoblastoma.
Centromere protein E as a novel biomarker and potential therapeutic target for retinoblastoma.
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着丝粒蛋白 E 作为视网膜母细胞瘤的新型生物标志物和潜在治疗靶点
DOI：
10.1080/21655979.2021.1972080
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发表时间：
2021-12
期刊：
影响因子：
4.9
通讯作者：
Sun X
中科院分区：
文献类型：
--
作者：
Shi K;Zhu X;Wu J;Chen Y;Zhang J;Sun X
视网膜母细胞瘤是儿童期最常见的眼内恶性肿瘤。目前，对于转移性视网膜母细胞瘤没有有效的治疗。我们利用来自公共数据库的三个数据集研究了视网膜母细胞瘤的潜在生物标志物。功能富集分析，包括基因本体论、基因和基因组的京都百科全书、基因集富集分析和变异分析，提示视网膜母细胞瘤差异表达基因在加速细胞周期事件中富集。蛋白质相互作用分析构建了由6个中心基因组成的网络，包括苯并咪唑1（BUB 1）、细胞周期蛋白依赖性激酶1（CDK 1）、着丝粒蛋白E（CENPE）、驱动蛋白家族成员20 A（KIF20 A）、PDZ结合激酶（PBK）和xklp2靶蛋白（TPX2）。药敏分析显示奈拉滨与5个hub基因呈正相关。所有六个基因在六种免疫亚型中表达不同，并且与大多数人类癌症类型中的干性指数呈正相关。由于CENPE是视网膜母细胞瘤中已知最少的枢纽基因，我们进一步分析了调节CENPE的潜在非编码RNA和转录因子，并建立了竞争性内源RNA和转录因子的相互作用网络。在CENPE高表达的样本中，免疫细胞浸润，尤其是血浆和B细胞的浸润增强。泛癌分析表明，CENPE在广泛的人类肿瘤中高度表达。体外验证显示，CENPE在视网膜母细胞瘤细胞中在mRNA和蛋白水平上均显著上调。总之，CENPE与其他枢纽基因沿着，可以作为视网膜母细胞瘤的潜在生物标志物和干预靶点。
Retinoblastoma is the most common intraocular malignancy during childhood. Currently, there is no effective treatment for metastatic retinoblastoma. We investigated potential biomarkers of retinoblastoma by utilizing three datasets from a public database. Functional enrichment analysis, including gene ontology, Kyoto encyclopedia of genes and genomes, gene set enrichment analysis and variation analysis, suggested that differentially expressed genes in retinoblastoma were enriched in accelerated cell cycle events. Protein-protein interaction analysis constructed a network consisting of six hub genes, including benzimidazoles 1 (BUB1), cyclin dependent kinase 1 (CDK1), centromere protein E (CENPE), kinesin family member 20A (KIF20A), PDZ binding kinase (PBK), and targeting protein for xklp2 (TPX2). Drug sensitivity analysis showed that nelarabine was positively correlated with five hub genes. All six genes were expressed differently in six immune subtypes and were positively correlated with stemness indices in most human cancer types. Since CENPE is the least known hub gene in retinoblastoma, we further analyzed the potential non-coding RNAs and transcription factors that regulate CENPE and built interaction networks of competing endogenous RNA and transcription factors. Immune cell infiltration, especially by plasma and B cells, was enhanced in samples with high CENPE expression. Pan-cancer analysis illustrated that CENPE was highly expressed in a wide range of human tumors. In vitro validation revealed that CENPE was significantly upregulated at both the mRNA and protein levels in retinoblastoma cells. In conclusion, CENPE, along with other hub genes, could serve as a potential biomarker and intervention target for retinoblastoma.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
168.9
作者：
Dimaras, Helen;Kimani, Kahaki;Gallie, Brenda L.
通讯作者：
Gallie, Brenda L.
DOI：
10.1073/pnas.090102397
发表时间：
2000-05-09
影响因子：
11.1
作者：
Gaudet, S;Branton, D;Lue, RA
通讯作者：
Lue, RA
影响因子：
3
作者：
Bader, GD;Hogue, CW
通讯作者：
Hogue, CW
影响因子：
6
作者：
Hudson, Lauren E.;Mendoza, Pia;Grossniklaus, Hans E.
通讯作者：
Grossniklaus, Hans E.