The upregulation and transcriptional regulatory mechanisms of Extra spindle pole bodies like 1 in bladder cancer: An...

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Investigating the expression and transcriptional regulation of Extra Spindle Pole Bodies Like 1 (ESPL1) in bladder cancer (BC) is crucial for understanding disease mechanisms.

Purpose of the Study:

• To explore the expression level and transcriptional regulation mechanism of ESPL1 in bladder cancer.
• To identify potential upstream regulatory factors and molecular pathways associated with ESPL1 in BC.
• To evaluate the potential of ESPL1 and miR-299-5p as diagnostic and prognostic biomarkers for BC.

Main Methods:

• Analysis of ESPL1 mRNA and protein expression in large-scale multicentre BC samples (n=1391) and validation (n=202).
• Single-cell sequencing (scRNA-seq) and enrichment analysis to determine ESPL1 distribution and molecular functions.
• Chromatin accessibility (ATAC-seq), transcription factor binding (ChIP-seq), and 3D genome structure (Hi-C) data analysis to identify upstream regulators and epigenetic mechanisms.
• Immune-related analysis, drug sensitivity assessment, molecular docking, and prediction of upstream microRNAs (miRNAs) and binding sites.
• Evaluation of miR-299-5p expression in blood (n=6625) and tissues (n=537) for early screening efficacy.

Main Results:

• ESPL1 was significantly overexpressed at both mRNA and protein levels in BC tissues.
• ESPL1 is primarily expressed in BC epithelial cells and coexpressed genes are enriched in cell cycle pathways, suggesting involvement in signaling pathways like Hippo, ErbB, PI3K-Akt, and Ras.
• Three transcription factors (H2AZ, IRF5, HIF1A) and enhancer-promoter loops were identified upstream of ESPL1, correlating with immune cell infiltration and affecting sensitivity to paclitaxel and gemcitabine.
• miR-299-5p was found to be downregulated in BC blood and tissues, indicating its potential as an early screening biomarker.

Conclusions:

• Upregulated ESPL1 in BC, particularly in epithelial cells, is linked to upstream transcription factors and regulatory elements, suggesting a cancer-promoting role.
• ESPL1 may serve as an immune-related predictive and diagnostic marker for BC, influencing patient response to drug therapy.
• Downregulated miR-299-5p in BC blood and tissues presents a promising novel marker for early cancer detection.