碱性螺旋-环-螺旋 ARNT 样 2 (ARNTL2) 是一种控制昼夜节律的转录因子。大量研究已经证明 ARNTL2 在人类恶性肿瘤中具有致癌作用，但其潜在机制仍知之甚少。我们的目的是研究ARNTL2在膀胱癌（BLCA）中的意义。利用免疫组织化学染色、免疫印迹和TCGA数据库分析ARNTL2、烯醇化酶1（ENO1）和溶质载体家族31成员1（SLC31A1）在膀胱癌中的临床相关性。 BLCA。通过细胞增殖测定、细胞凋亡、集落形成和异种移植肿瘤发生来探索 ARNTL2 的功能。通过 RT-qPCR、免疫印迹和荧光素酶测定研究了 ARNTL2 驱动 BLCA 发育的分子机制。通过测量葡萄糖消耗和乳酸产生来检查糖酵解。使用指定的检测试剂盒评估ENO1活性。ARNTL2的过表达通过抑制细胞凋亡和增强糖酵解促进BLCA细胞的增殖和肿瘤发生。 SLC31A1、ENO1 的上调以及 SLC31A1 介导的 ENO1 活性的增强对于 ARNTL2 触发的糖酵解和 BLCA 细胞的恶性生长至关重要。 BLCA 患者中 ARNTL2 与 SLC31A1 和 ENO1 呈正相关。 ARNTL2、SLC31A1或ENO1的高表达预示着BLCA患者的不良预后。 SLC31A1的耗竭和糖酵解的抑制完全削弱了BLCA细胞的生长能力。 总之，ARNTL2以不依赖于SLC31A1和依赖于SLC31A1的方式通过激活ENO1介导的糖酵解来促进BLCA的进展。抑制 SLC31A1 和糖酵解可能是治疗 ARNTL2 过度表达 BLCA 患者的理想方法。版权所有 © 2024。由 Elsevier Inc. 出版。

Basic helix-loop-helix ARNT like 2 (ARNTL2) is a transcription factor that controls the circadian rhythm. Amounts of studies have demonstrated the carcinogenic function of ARNTL2 in human malignant tumors albeit the underlying mechanisms remain poorly understood. We aimed to study the significance of ARNTL2 in bladder cancer (BLCA).Immunohistochemical staining, immunoblotting and the database from TCGA were used to analyze the clinical relevance of ARNTL2, enolase 1 (ENO1) and solute carrier family 31 member 1 (SLC31A1) in BLCA. The function of ARNTL2 was explored by cell proliferation assay, apoptosis, colony formation and xenografted tumorigenesis. The molecular mechanisms of ARNTL2-driving BLCA development were investigated by RT-qPCR, immunoblotting and luciferase assays. Glycolysis was checked by measuring glucose consumption and lactate production. ENO1 activity was assessed by using indicated assay kit.Overexpression of ARNTL2 facilitates the proliferation and tumorigenesis of BLCA cells through suppression of apoptosis and enhancement of glycolysis. Up-regulation of SLC31A1, ENO1, and enhancement of SLC31A1-mediated ENO1 activity were critical for ARNTL2-triggered glycolysis and malignant growth in BLCA cells. ARNTL2 was positively correlated with SLC31A1 and ENO1 in BLCA patients. High expression of ARNTL2, SLC31A1 or ENO1 predicted the poor prognosis of BLCA patients. Depletion of SLC31A1 and inhibition of glycolysis completely blunted the growth ability of BLCA cells.In summary, ARNTL2 facilitates the progression of BLCA via activating ENO1-mediated glycolysis in a SLC31A1-independent and -dependent manner. Inhibiting SLC31A1 and glycolysis may be an aspirational approach for the treatment of BLCA patients with overexpression of ARNTL2.Copyright © 2024. Published by Elsevier Inc.