Primary microcephaly gene CENPE is a novel biomarker and potential therapeutic target for non-WNT/non-SHH medulloblastoma

作者：Huangyi Fang, Yusong Zhang, Chengyin Lin, Zhenkai Sun, Wei Wen, Hansong Sheng, Jian Lin · 发表于：Frontiers in Immunology · 年份：2023 · DOI：10.3389/fimmu.2023.1227143 · 被引用次数：8 · 研究领域：Microtubule and mitosis dynamics、Glioma Diagnosis and Treatment、Hedgehog Signaling Pathway Studies

Background 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. Methods 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. Results 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 CENP...