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敲低同源盒蛋白 B5(HOXB5)通过抑制 Wnt/β-连环蛋白通路抑制非小细胞肺癌细胞的增殖、迁移和侵袭。

Knockdown of Homeobox B5 (HOXB5) Inhibits Cell Proliferation, Migration, and Invasion in Non-Small Cell Lung Cancer Cells Through Inactivation of the Wnt/β-Catenin Pathway.

机构信息

Department of Respiratory Disease, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, Zhejiang Province, P.R. China.

出版信息

Oncol Res. 2018 Jan 19;26(1):37-44. doi: 10.3727/096504017X14900530835262. Epub 2017 Mar 23.

Abstract

Homeobox B5 (HOXB5), a member of the HOX gene family, has been shown to play an important role in tumor progression. However, the expression and functional role of HOXB5 in human non-small cell lung cancer (NSCLC) have not been defined. Thus, the purpose of this study was to elucidate the expression and functional role of HOXB5 in human NSCLC. Our results showed that HOXB5 expression was elevated in human NSCLC tissues and cell lines. The in vitro experiments demonstrated that knockdown of HOXB5 inhibited proliferation, migration, and invasion and prevented the EMT phenotype in NSCLC cells. In vivo experiments indicated that knockdown of HOXB5 attenuated the growth of NSCLC xenografts in vivo. Furthermore, knockdown of HOXB5 suppressed the protein expression levels of β-catenin and its downstream targets c-Myc and cyclin D1 in A549 cells. Taken together, for the first time we have shown that knockdown of HOXB5 significantly inhibited NSCLC cell proliferation, invasion, metastasis, and EMT, partly through the Wnt/β-catenin signaling pathway. These findings suggest that HOXB5 may be a novel therapeutic target for the treatment of NSCLC.

摘要

Homeobox B5(HOXB5)是 HOX 基因家族的成员,已被证明在肿瘤进展中发挥重要作用。然而,HOXB5 在人非小细胞肺癌(NSCLC)中的表达和功能作用尚未确定。因此,本研究旨在阐明 HOXB5 在人 NSCLC 中的表达和功能作用。

我们的研究结果表明,HOXB5 在人 NSCLC 组织和细胞系中表达上调。体外实验表明,HOXB5 敲低抑制 NSCLC 细胞的增殖、迁移和侵袭,并阻止 EMT 表型。体内实验表明,HOXB5 敲低减弱了 NSCLC 异种移植瘤在体内的生长。此外,HOXB5 敲低抑制了 A549 细胞中β-catenin 及其下游靶标 c-Myc 和 cyclin D1 的蛋白表达水平。

综上所述,我们首次表明,HOXB5 敲低显著抑制 NSCLC 细胞的增殖、侵袭、转移和 EMT,部分通过 Wnt/β-catenin 信号通路。这些发现表明 HOXB5 可能是治疗 NSCLC 的一种新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ca1/7844563/90273bf1093e/OR-26-037-g001.jpg

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