E2F1-mediated ESPL1 transcriptional activation predicts poor prognosis and promotes the proliferation of leiomyosarcoma.

IF 2.5 4区医学 Q2 PATHOLOGY

Cytojournal Pub Date : 2025-01-08 eCollection Date: 2025-01-01 DOI:10.25259/Cytojournal_178_2024

Xiaojuan Yang, Guihua Miao, Qin Wang, Qin Yu, Qinsheng Hu, Gang Tan

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引用次数: 0

Abstract

Objective: Soft tissue and bone cancers, collectively known as sarcomas, constitute a diverse array of uncommon tumors originating from connective tissues. Among sarcomas, leiomyosarcoma (LMS) is one of the most frequently encountered subtypes. This study aims to investigate the expression, clinical significance, biological regulation, and dysregulation mechanisms of extra spindle pole bodies like 1 (ESPL1), a gene critical for cell cycle regulation in LMS.

Material and methods: Bioinformatics analysis was performed using the data from The Cancer Genome Atlas-Sarcoma and Genotype-Tissue Expression datasets. Functional experiments to assess cell proliferation and the cell cycle were performed in LMS cells (SK-LMS-1) after ESPL1 knockdown. Bioinformatics analyses were conducted to identify the potential transcriptional regulators of ESPL1. The regulatory relationship between ESPL1 and the E2F transcription factor 1 (E2F1) was validated through the various molecular assays.

Results: ESPL1 is significantly overexpressed in LMS compared with normal muscle tissue. High ESPL1 expression is associated with a shorter progression-free interval (PFI) in sarcoma patients, particularly in the LMS subset. ESPL1 expression might be an independent prognostic factor for poor overall survival and PFI in LMS patients. Functional studies in the LMS cell line SK-LMS-1 demonstrated that ESPL1 knockdown slowed cell proliferation and increased G2/M cell cycle arrest, suggesting its crucial role in maintaining LMS cell viability and genomic integrity. Further bioinformatics analysis identified the E2F1 transcription factor as a key regulator of ESPL1 expression in LMS. Mechanistic investigations demonstrated that E2F1 interacts with the ESPL1 promoter, leading to transcriptional activation.

Conclusion: These findings highlight the ESPL1-E2F1 axis as a potential prognostic biomarker and therapeutic target in LMS.

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来源期刊

Cytojournal PATHOLOGY-

CiteScore

2.20

自引率

42.10%

发文量

审稿时长

>12 weeks

期刊介绍： The CytoJournal is an open-access peer-reviewed journal committed to publishing high-quality articles in the field of Diagnostic Cytopathology including Molecular aspects. The journal is owned by the Cytopathology Foundation and published by the Scientific Scholar.