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FOXJ1促进膀胱癌细胞生长并调节瓦伯格效应。

FOXJ1 promotes bladder cancer cell growth and regulates Warburg effect.

作者信息

Xian Shaozhong, Shang Donghao, Kong Guangqi, Tian Ye

机构信息

Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China; Department of Urology, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149, China.

Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.

出版信息

Biochem Biophys Res Commun. 2018 Jan 1;495(1):988-994. doi: 10.1016/j.bbrc.2017.11.063. Epub 2017 Nov 10.

Abstract

Forkhead Box J1 (FOXJ1) which belongs to Fox gene family, plays complex and crucial roles in processes of development, organogenesis, regulation of the immune system, as well as progression of several malignancies. However, how FOXJ1 functions in bladder cancer remains unclear. Here, we report that FOXJ1 is upregulated in most bladder cancer patients, and predicts poor clinical outcomes. FOXJ1 facilitates bladder cancer cell proliferation and colony formation. FOXJ1 knockdown suppresses bladder tumor growth in nude mice. Mechanistically, FOXJ1 enhances glycolysis by increasing glucose uptake, lactate production and extracellular acidification rate (ECAR), and decreasing ATP generation and oxygen consumption rate (OCR) in bladder cancer cells. Our findings provide clues regarding the role of FOXJ1 as a tumor inducer in bladder cancer and an enhancer in glycolysis. Targeting FOXJ1 could be a potential therapeutic strategy in bladder cancer.

摘要

叉头框J1(FOXJ1)属于Fox基因家族,在发育、器官形成、免疫系统调节以及多种恶性肿瘤的进展过程中发挥着复杂而关键的作用。然而,FOXJ1在膀胱癌中的作用机制尚不清楚。在此,我们报告FOXJ1在大多数膀胱癌患者中上调,并预示不良的临床预后。FOXJ1促进膀胱癌细胞增殖和集落形成。敲低FOXJ1可抑制裸鼠膀胱肿瘤生长。机制上,FOXJ1通过增加葡萄糖摄取、乳酸生成和细胞外酸化率(ECAR),并降低膀胱癌细胞中的ATP生成和氧消耗率(OCR)来增强糖酵解。我们的研究结果为FOXJ1作为膀胱癌中的肿瘤诱导因子和糖酵解增强剂的作用提供了线索。靶向FOXJ1可能是膀胱癌的一种潜在治疗策略。

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