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

Huangyi Fang; Yusong Zhang; Chengyin Lin; Zhenkai Sun; Wei Wen; Hansong Sheng; Jian Lin

doi:10.3389/fimmu.2023.1227143

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

Front Immunol. 2023 Aug 1:14:1227143. doi: 10.3389/fimmu.2023.1227143. eCollection 2023.

Authors

Huangyi Fang^{1

2}, Yusong Zhang^{1

3}, Chengyin Lin¹, Zhenkai Sun^{1

2}, Wei Wen^{1

2}, Hansong Sheng^{1

2}, Jian Lin^{1

2

4}

Affiliations

¹ Wenzhou Medical University, Wenzhou, China.
² Department of Neurosurgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
³ Department of Surgery, The First People's Hospital of Jiashan, Jiaxing, China.
⁴ The Key Laboratory of Pediatric Hematology and Oncology Diseases of Wenzhou, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Abstract

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 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.

Conclusion: 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.

Keywords: CENPE; bioinformatics analysis; cell cycle; microcephaly; non-WNT/non-SHH medulloblastoma; p53.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Cerebellar Neoplasms* / genetics
Cerebellar Neoplasms* / therapy
Humans
Medulloblastoma* / genetics
Medulloblastoma* / therapy
Microcephaly*
Tumor Microenvironment / genetics
Tumor Suppressor Protein p53

Substances

Tumor Suppressor Protein p53
Biomarkers

Grants and funding

This work was supported by the Wenzhou Municipal Science & Technology Bureau (Nos. ZY2021007), Science Technology Department of Zhejiang Province (Nos. IGF22H160060) and Health Science and Technology Plan of Zhejiang Province (Nos. 2021KY794 and 2023KY147).