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BZW2 基因敲低可诱导肌层浸润性膀胱癌细胞生长抑制、G1 期阻滞和凋亡:基因芯片通路分析。

BZW2 gene knockdown induces cell growth inhibition, G1 arrest and apoptosis in muscle-invasive bladder cancers: A microarray pathway analysis.

机构信息

Department of Urology Surgery, Dalian Municipal Central Hospital, Dalian, China.

Department of Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.

出版信息

J Cell Mol Med. 2019 Jun;23(6):3905-3915. doi: 10.1111/jcmm.14266. Epub 2019 Apr 1.

Abstract

Bladder cancer is among the most common cancers all over the world. The function of basic leucine zipper and W2 domains 2 (BZW2) in tumour progression has been reported. However, the biological function of BZW2 in muscle-invasive bladder cancers (MIBCs) remains to be determined. The aim of the present study was to reveal the expression and roles of BZW2 in human MIBCs and to explore the molecular mechanisms underlying these functions. Clinically, BZW2 expression was higher in MIBC tissues than the adjacent non-tumour tissues. Knocking down BZW2 using shRNA inhibited cell proliferation and G1/S cell cycle progression in vitro, and induced apoptosis in both 5637 and T24 cells. Moreover, in vivo studies with mice xenograft models confirmed the anti-proliferative effects of BZW2-knockdown, providing a future therapeutic target. We also performed biochemical microarray analysis to identify the potential signalling pathways, disease states and functions which could be affected by suppressing BZW2 in MIBC cells. Collectively, our findings suggest BZW2 has an oncogenic role in MIBCs and serves as a promising target for molecular diagnosis and gene therapy.

摘要

膀胱癌是全世界最常见的癌症之一。已有报道称基本亮氨酸拉链和 W2 结构域 2(BZW2)在肿瘤进展中的作用。然而,BZW2 在肌层浸润性膀胱癌(MIBC)中的生物学功能仍有待确定。本研究旨在揭示 BZW2 在人 MIBC 中的表达和作用,并探讨这些功能的分子机制。临床上,BZW2 在 MIBC 组织中的表达高于相邻非肿瘤组织。使用 shRNA 敲低 BZW2 在体外抑制细胞增殖和 G1/S 细胞周期进程,并诱导 5637 和 T24 细胞凋亡。此外,在小鼠异种移植模型的体内研究中证实了 BZW2 敲低的抗增殖作用,为未来的治疗提供了靶点。我们还进行了生化微阵列分析,以确定抑制 MIBC 细胞中的 BZW2 可能影响的潜在信号通路、疾病状态和功能。综上所述,我们的研究结果表明 BZW2 在 MIBC 中具有致癌作用,是分子诊断和基因治疗的有前途的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a49a/6533564/218216d27f66/JCMM-23-3905-g001.jpg

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