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叉头框蛋白 F1 可作为一种新型的预后生物标志物,并在膀胱癌中诱导半胱氨酸天冬氨酸蛋白酶依赖性细胞凋亡。

Forkhead box F1 functions as a novel prognostic biomarker and induces caspase‑dependent apoptosis in bladder cancer.

机构信息

Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.

出版信息

Oncol Rep. 2023 Sep;50(3). doi: 10.3892/or.2023.8610. Epub 2023 Aug 4.

Abstract

The downregulated expression of forkhead box F1 (FOXF1) has been found in many malignant tumors but no research was done in bladder cancer (BC). The present study aimed to investigate the prognostic value and antitumor effects of FOXF1 in patients with BC. Herein, a retrospectively recruited BC cohort and public datasets were utilized to identify the predictive ability of FOXF1 and determine its association with the clinical characteristics of BC patients. It was found that the expression level of FOXF1 was notably lower in BC tissues than in para‑cancerous mucosae. Low FOXF1 expression was associated with unfavorable clinicopathological features and poor prognosis. Furthermore, in BC cells, the mRNA and protein expression levels of FOXF1 were examined using reverse transcription‑quantitative PCR and western blot analysis. Cell viability was examined using Cell Counting Kit‑8, EdU and clonogenic capacity assays. Cell apoptosis was detected using flow cytometry. The results revealed that the activation of FOXF1 impaired cell viability and induced apoptosis in BC. The antitumor effects of FOXF1 were also validated using animal models. Subsequently, caspase‑3 was spotted as a downstream gene of FOXF1 by using RNA sequencing and protein‑protein interaction analyses. FOXF1 inhibited proliferation and induced apoptosis of BC cells via caspase signaling pathway. The present study demonstrates the expression patterns, prognostic predictive ability and antitumor effects of FOXF1 in BC. FOXF1 is a favorable biomarker for predicting clinical outcomes in patients with BC and represents a potential therapeutic target.

摘要

叉头框蛋白 F1(FOXF1)的下调表达已在许多恶性肿瘤中发现,但在膀胱癌(BC)中尚未进行研究。本研究旨在探讨 FOXF1 在 BC 患者中的预后价值和抗肿瘤作用。在此,利用回顾性招募的 BC 队列和公共数据集来确定 FOXF1 的预测能力,并确定其与 BC 患者临床特征的关联。结果发现,FOXF1 在 BC 组织中的表达水平明显低于癌旁黏膜。FOXF1 低表达与不良临床病理特征和预后不良相关。此外,在 BC 细胞中,通过逆转录定量 PCR 和 Western blot 分析检测 FOXF1 的 mRNA 和蛋白表达水平。使用细胞计数试剂盒-8、EdU 和集落形成能力测定法检测细胞活力。通过流式细胞术检测细胞凋亡。结果表明,FOXF1 的激活可损害 BC 细胞的活力并诱导其凋亡。使用动物模型也验证了 FOXF1 的抗肿瘤作用。随后,通过 RNA 测序和蛋白质-蛋白质相互作用分析,将半胱天冬酶-3 鉴定为 FOXF1 的下游基因。FOXF1 通过半胱天冬酶信号通路抑制 BC 细胞的增殖并诱导其凋亡。本研究表明 FOXF1 在 BC 中的表达模式、预后预测能力和抗肿瘤作用。FOXF1 是预测 BC 患者临床结局的有利生物标志物,代表了一个潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b677/10433446/d025e327d220/or-50-03-08610-g01.jpg

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