RHBDD1 通过激活 Wnt/β-catenin 信号通路促进胃癌细胞的生长和干性特征。
RHBDD1 Promotes the Growth and Stemness Characteristics of Gastric Cancer Cells by Activating Wnt/β-catenin Signaling Pathway.
机构信息
Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical, Chongqing, 400010, China.
Department of Ultrasound, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400010, China.
出版信息
Curr Stem Cell Res Ther. 2024;19(7):1021-1028. doi: 10.2174/011574888X259932231010112521.
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 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 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.
背景
胃癌（GC）威胁着公众健康，每年至少有 100 万新发病例。菱形结构域包含蛋白 1（RHBDD1）已被鉴定为调节癌细胞的增殖、迁移和转移。然而，RHBDD1 在 GC 中的作用尚未阐明。
目的
本研究旨在探讨 RHBDD1 对 GC 生长、转移和干性特征的作用。
方法
从 TCGA 数据库分析 RHBDD1 的表达。qRT-PCR 用于评估 RHBDD1 的转录水平。Western blot 用于评估 RHBDD1、CD133、CD44、Nanog、β-catenin 和 c-myc 的蛋白表达。集落形成实验和 Transwell 实验分别用于评估 NCI-N87 细胞的生长和转移。球形成实验用于研究干性特征。裸鼠异种移植模型和免疫组织化学（IHC）用于评估 GC 的生长。
结果
RHBDD1 在 GC 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 激活 Wnt/β-catenin 通路，促进β-catenin/c-myc 的表达，并诱导β-catenin 向核内易位。RHBDD1 敲低抑制裸鼠异种移植模型中 GC 的生长。
结论
RHBDD1 在 GC 中高表达，其敲低通过激活 Wnt/β-catenin 通路抑制 GC 细胞的生长、转移和干性特征，表明 RHBDD1 有可能成为 GC 治疗的新靶点。
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