环状指蛋白 43 通过抑制 Wnt/β-连环蛋白通路抑制三阴性乳腺癌的进展。

RNF43 Suppressed Triple-Negative Breast Cancer Progression by Inhibiting Wnt/beta-Catenin Pathway.

机构信息

Department of Thyroid and Breast Surgery, Beilun People's Hospital, Ningbo, Zhejiang, China

No.2 Outpatient Department, 908 Hospital of PLA Joint Logistic Support Force, Nanchang, Jiangxi, China.

出版信息

Ann Clin Lab Sci. 2023 Jan;53(1):21-29.

PMID:36889779

Abstract

OBJECTIVE

Triple-negative breast cancer (TNBC) is a subtype with high invasiveness. Due to lacking specific and effective therapies, it is necessary to explore the mechanism of TNBC progression and search for new therapeutic targets.

METHODS

Data from the GEPIA2 database was analyzed to explore RNF43 expression in each subtype of breast cancer. RNF43 expression in TNBC tissue and cell lines was determined by RT-qPCR. biological function analyses including MTT assay, colony formation assay, wound-healing assay and Transwell assay were conducted to explore the role of RNF43 in TNBC. In addition, the markers of epithelial-mesenchymal transition (EMT) were detected by western blot. The expression of β-Catenin and its downstream effectors were also detected.

RESULTS

Data from the GEPIA2 database indicated that RNF43 expression was lower in tumor tissue compared to paired adjacent tissue in TNBC. In addition, RNF43 expression in TNBC was lower than in other subtypes of breast cancer. Consistently, down-regulation of RNF43 expression in TNBC tissue and cell lines was observed. Overexpressing RNF43 attenuated the proliferation and migration of TNBC cells. Depletion of RNF43 showed the opposite effect, confirming that RNF43 played an anti-oncogenic role in TNBC. In addition, RNF43 suppressed several markers of EMT. Furthermore, RNF43 restrained the expression of β-Catenin and its downstream effectors, implying RNF43 exerted the suppressive role in TNBC by inhibiting the β-Catenin pathway.

CONCLUSIONS

This study demonstrated that the RNF43-β-Catenin axis attenuated TNBC progression, which might provide novel therapeutic targets for TNBC.

摘要

目的

三阴性乳腺癌（TNBC）是一种侵袭性较高的亚型。由于缺乏特异性和有效的治疗方法，因此有必要探索 TNBC 进展的机制并寻找新的治疗靶点。

方法

分析 GEPIA2 数据库中的数据，以探讨 RNF43 在乳腺癌各亚型中的表达情况。通过 RT-qPCR 测定 TNBC 组织和细胞系中的 RNF43 表达。通过 MTT assay、集落形成 assay、划痕愈合 assay 和 Transwell assay 进行生物功能分析，以探讨 RNF43 在 TNBC 中的作用。此外，通过 Western blot 检测上皮间质转化（EMT）的标志物。还检测了β-Catenin 及其下游效应物的表达。

结果

GEPIA2 数据库中的数据表明，TNBC 肿瘤组织中的 RNF43 表达低于配对的相邻组织。此外，与其他乳腺癌亚型相比，TNBC 中的 RNF43 表达水平更低。同样，观察到 TNBC 组织和细胞系中 RNF43 表达下调。过表达 RNF43 可减弱 TNBC 细胞的增殖和迁移。RNF43 耗竭则显示出相反的效果，证实 RNF43 在 TNBC 中发挥抑癌作用。此外，RNF43 抑制了 EMT 的几个标志物。此外，RNF43 抑制了β-Catenin 及其下游效应物的表达，表明 RNF43 通过抑制β-Catenin 通路发挥对 TNBC 的抑制作用。