RHBDD1通过激活Wnt/β-catenin信号通路促进癌症细胞生长和应激特性。

Yingxue Yang, Yuan Yuan, Boning Xia
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引用次数: 0

摘要

背景:癌症(GC)正在威胁公众健康,每年至少有100万例新病例报告。含菱形结构域的蛋白1(RHBDD1)已被鉴定为调节癌症细胞的增殖、迁移和转移。然而,RHBDD1在GC中的作用尚未阐明。目的:研究RHBDD1在胃癌生长、转移和干性中的作用。方法:从TCGA数据库中分析RHBDD1的表达。进行qRT-PCR以评估RHBDD1的转录水平。用蛋白质印迹法检测RHBDD1、CD133、CD44、Nanog、β-catenin和c-myc的蛋白表达。分别进行集落形成测定和transwell测定以评估NCI-N87细胞的生长和转移。通过球体形成实验研究干度特性。采用裸鼠异种移植模型和免疫组织化学(IHC)方法评价GC在体内的生长情况。结果:RHBDD1在胃癌细胞和临床组织中表达升高。RHBDD1的表达与GC细胞的增殖和转移呈正相关。RHBDD1敲低抑制CD133、CD44和Nanog的表达并减弱球体形成能力。RHBDD1通过促进β-catenin/c-myc的表达和诱导β-catenin易位进入细胞核来激活Wnt/β-catenin-通路。RHBDD1敲低抑制裸鼠异种移植模型中GC的生长。结论:RHBDD1在胃癌中高表达,其敲低通过激活Wnt/β-catenin通路抑制胃癌细胞的生长、转移和干性特征,表明RHBDD1有可能成为胃癌治疗的新靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
RHBDD1 Promotes the Growth and Stemness Characteristics of Gastric Cancer Cells by Activating Wnt/β-catenin Signaling Pathway.

Backgrounds: Gastric cancer (GC) is threatening public health, with at least one million new cases reported each year. Rhomboid domain-containing protein 1 (RHBDD1) has been identified to regulate the proliferation, migration, and metastasis of cancer cells. However, the role of RHBDD1 in GC has not been elucidated.

Objects: This study aimed to investigate the role of RHBDD1 on the growth, metastasis, and stemness characteristics of GC.

Methods: RHBDD1 expression was analyzed from the TCGA databank. qRT-PCR was conducted to evaluate the transcription level of RHBDD1. Western blots were used to evaluate the protein expression of RHBDD1, CD133, CD44, Nanog, β-catenin and c-myc. Colony formation assay and transwell assay were conducted to evaluate the growth and metastasis of NCI-N87 cells, respectively. Sphere-forming assay was performed to study the stemness characteristics. The nude mice xenotransplantation model and immunohistochemistry (IHC) were performed to evaluate the growth of GC in vivo. Results: RHBDD1 expression is elevated in GC cells and clinical tissues. RHBDD1 expression is positively associated with cell proliferation and metastasis of GC cells. RHBDD1 knockdown suppresses the expression of CD133, CD44 and Nanog and attenuates sphere-forming ability. RHBDD1 activates the Wnt/β-catenin pathway via promoting the expression of β-catenin / c-myc and inducing β-catenin translocation into nuclear. RHBDD1 knockdown inhibits the growth of GC in nude mice xenotransplantation model.

Conclusion: RHBDD1 is highly expressed in GC, and its knockdown inhibits the growth, metastasis and stemness characteristics of GC cells through activating the Wnt/β-catenin pathway, suggesting that RHBDD1 has the potential to be a novel therapeutic target for GC treatment.

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