POLE2 预后枢纽基因通过 PI3K/AKT 信号通路促进膀胱癌细胞生长。

The Prognostic Hub Gene POLE2 Promotes BLCA Cell Growth via the PI3K/AKT Signaling Pathway.

机构信息

Department of Urology, Minhang Hospital, Fudan University, 170 Xin-Song Road, Shanghai, 201199, China.

出版信息

Comb Chem High Throughput Screen. 2024;27(13):1984-1998. doi: 10.2174/0113862073273633231113060429.

DOI:10.2174/0113862073273633231113060429

PMID:38963027

Abstract

BACKGROUND

BLCA is a common urothelial malignancy characterized by a high recurrence rate. Despite its prevalence, the molecular mechanisms underlying its development remain unclear.

AIMS

This study aimed to explore new prognostic biomarkers and investigate the underlying mechanism of bladder cancer (BLCA).

OBJECTIVE

The objective of this study is to identify key prognostic biomarkers for BLCA and to elucidate their roles in the disease.

METHODS

We first collected the overlapping DEGs from GSE42089 and TCGA-BLCA samples for the subsequent weighted gene co-expression network analysis (WGCNA) to find a key module. Then, key module genes were analyzed by the MCODE algorithm, prognostic risk model, expression and immunohistochemical staining to identify the prognostic hub gene. Finally, the hub gene was subjected to clinical feature analysis, as well as cellular function assays.

RESULTS

In WGCNA on 1037 overlapping genes, the blue module was the key module. After a series of bioinformatics analyses, POLE2 was identified as a prognostic hub gene in BLCA from potential genes (TROAP, POLE2, ANLN, and E2F8). POLE2 level was increased in BLCA and related to different clinical features of BLCA patients. Cellular assays showed that si-POLE2 inhibited BLCA proliferation, and si-POLE2+ 740Y-P in BLCA cells up-regulated the PI3K and AKT protein levels.

CONCLUSION

In conclusion, POLE2 was identified to be a promising prognostic biomarker as an oncogene in BLCA. It was also found that POLE2 exerts a promoting function by the PI3K/AKT signaling pathway in BLCA.

摘要

背景

BLCA 是一种常见的尿路上皮恶性肿瘤，其特点是复发率高。尽管它很常见，但它的发展的分子机制仍不清楚。

目的

本研究旨在探索新的预后生物标志物，并研究膀胱癌（BLCA）的潜在机制。

目的

本研究旨在确定 BLCA 的关键预后生物标志物，并阐明它们在疾病中的作用。

方法

我们首先从 GSE42089 和 TCGA-BLCA 样本中收集重叠的 DEGs，用于随后的加权基因共表达网络分析（WGCNA），以找到关键模块。然后，通过 MCODE 算法、预后风险模型、表达和免疫组织化学染色分析关键模块基因，以确定预后关键基因。最后，对关键基因进行临床特征分析和细胞功能测定。

结果

在对 1037 个重叠基因进行 WGCNA 分析时，蓝色模块是关键模块。经过一系列生物信息学分析，POLE2 被确定为 BLCA 中的一个潜在基因（TROAP、POLE2、ANLN 和 E2F8）中的预后关键基因。POLE2 在 BLCA 中表达上调，并与 BLCA 患者的不同临床特征相关。细胞实验表明，si-POLE2 抑制 BLCA 增殖，而 si-POLE2+740Y-P 在 BLCA 细胞中上调 PI3K 和 AKT 蛋白水平。