非WNT/non-SHH型髓母细胞瘤（MB）是髓母细胞瘤中遗传异质性最高的亚型之一，目前的治疗策略效果不佳且存在明显的副作用。作为Centromeric protein (CENP)家族的成员，Centromeric protein E (CENPE)是一个微管加端定位的着丝粒蛋白激酶。CENPE的杂合突变可导致原发性小头畸形综合征。有报道称在MB中CENPE表达上调，但其在MB发展中的作用尚不清楚。我们从GEO数据库下载相关RNA序列数据和相匹配的临床信息。生物信息学分析包括差异基因表达分析、Kaplan-Meier生存分析、诺莫图分析、ROC曲线分析、免疫细胞浸润分析和基因功能富集分析。此外，通过在体外实验使用CENPE特异性siRNA验证了CENPE表达对非WNT/non-SHH MB的细胞增殖、细胞周期和p53信号通路的影响。与正常组织相比，CENPE在MB组织中高表达，并且作为非WNT/non-SHH MB患者存活的独立预后因子。诺莫图分析和ROC曲线进一步证实了这些发现。同时，免疫细胞浸润分析显示CENPE可能参与非WNT/non-SHH MB的免疫应答和肿瘤微环境（TME）。此外，基因富集分析显示CENPE与非WNT/non-SHH MB的细胞周期和p53通路密切相关。体外实验验证显示抑制CENPE可以通过激活p53信号通路和阻断细胞周期来抑制细胞增殖。CENPE在非WNT/non-SHH MB中的表达与不良预后呈正相关。CENPE可能通过调节细胞周期、p53通路和免疫浸润影响肿瘤进展。因此，CENPE很有可能是非WNT/non-SHH MB的新生物标志物和潜在治疗靶点。 版权所有 © 2023 Fang, Zhang, Lin, Sun, Wen, Sheng和Lin。

Non-WNT/non-SHH medulloblastoma (MB) is one of the subtypes with the highest genetic heterogeneity in MB, and its current treatment strategies have unsatisfactory results and significant side effects. As a member of the centromere protein (CENP) family, centromeric protein E (CENPE) is a microtubule plus-end-directed kinetochore protein. Heterozygous mutations in CENPE can leads to primary microcephaly syndrome. It has been reported that CENPE is upregulated in MB, but its role in MB development is still unknown.We downloaded the relevant RNA seq data and matched clinical information from the GEO database. Bioinformatics analysis includes differential gene expression analysis, Kaplan-Meier survival analysis, nomogram analysis, ROC curve analysis, immune cell infiltration analysis, and gene function enrichment analysis. Moreover, the effects of CENPE expression on cell proliferation, cell cycle, and p53 signaling pathway of non-WNT/non-SHH MB were validated using CENPE specific siRNA in vitro experiments.Compared with normal tissues, CENPE was highly expressed in MB tissues and served as an independent prognostic factor for survival in non-WNT/non-SHH MB patients. The nomogram analysis and ROC curve further confirmed these findings. At the same time, immune cell infiltration analysis showed that CENPE may participate in the immune response and tumor microenvironment (TME) of non-WNT/non-SHH MB. In addition, gene enrichment analysis showed that CENPE was closely related to the cell cycle and p53 pathway in non-WNT/non-SHH MB. In vitro experimental validation showed that knockdown of CENPE inhibited cell proliferation by activating the p53 signaling pathway and blocking the cell cycle.The expression of CENPE in non-WNT/non-SHH MB was positively correlated with poor prognosis. CENPE may affect tumor progression by regulating cell cycle, p53 pathway, and immune infiltration. Hence, CENPE is highly likely a novel biomarker and potential therapeutic target for non-WNT/non-SHH MB.Copyright © 2023 Fang, Zhang, Lin, Sun, Wen, Sheng and Lin.