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通过小干扰RNA敲低RUVBL1表达对β-连环蛋白/淋巴细胞增强因子1信号通路的调控可抑制乳腺癌细胞的增殖、迁移和侵袭。

Regulation of the β‑catenin/LEF‑1 pathway by the siRNA knockdown of RUVBL1 expression inhibits breast cancer cell proliferation, migration and invasion.

作者信息

Zhang Xin, Cui Dingyuan, Sun Wei, Yang Guangfei, Wang Wen, Mi Chengrong

机构信息

School of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China.

Department of Ultrasound, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China.

出版信息

Oncol Rep. 2025 Feb;53(2). doi: 10.3892/or.2024.8855. Epub 2024 Dec 13.

Abstract

RUVBL1 is a protein characterized by its DNA‑dependent ATPase activity and DNA deconjugating enzyme function. It is a member of the ATPase (AAA+) protein family associated with various cellular processes. Available research confirms that the expression of RUVBL1 is upregulated in breast cancer (BRCA) cell lines; however, the mechanisms underlying its functional role in BRCA remain unclear. The β‑catenin/lymphoid enhancer factor‑1 (LEF‑1) pathway plays a crucial role in the occurrence and development of BRCA. The aim of the present study was to investigate whether RUVBL1 regulates the proliferation, migration and invasion of BRCA cells by participating in the β‑catenin/LEF‑1 signaling pathway. Reverse transcription‑quantitative PCR (RT‑qPCR) and western blot analysis were employed to compare the RUVBL1 expression levels between normal mammary epithelial cells (MCF‑10a) and BRCA cell lines (MDA‑MB‑231 and MCF‑7). Scratch, Cell Counting Kit‑8 and Transwell assays were utilized to assess the effects of RUVBL1 knockdown on the proliferation, migration and invasion of BRCA cells. Following the downregulation of RUVBL1 expression , western blot analysis and RT‑qPCR were conducted to investigate its role in regulating the β‑catenin/LEF‑1 pathway. The aforementioned experiments proved that the knockdown of RUVBL1 expression inhibited BRCA cell proliferative, migratory and invasive capabilities, modulating the β‑catenin/LEF‑1 pathway. Collectively, the findings of the present study provide preliminarily confirmation that RUVBL1 participates in the molecular mechanisms of the β‑catenin signaling pathway, which may provide a novel target for BRCA treatment.

摘要

RUVBL1是一种具有DNA依赖性ATP酶活性和DNA解偶联酶功能的蛋白质。它是与各种细胞过程相关的ATP酶(AAA+)蛋白家族的成员。现有研究证实,RUVBL1在乳腺癌(BRCA)细胞系中的表达上调;然而,其在BRCA中发挥功能作用的机制仍不清楚。β-连环蛋白/淋巴样增强因子-1(LEF-1)途径在BRCA的发生和发展中起关键作用。本研究的目的是探讨RUVBL1是否通过参与β-连环蛋白/LEF-1信号通路来调节BRCA细胞的增殖、迁移和侵袭。采用逆转录定量PCR(RT-qPCR)和蛋白质印迹分析比较正常乳腺上皮细胞(MCF-10a)与BRCA细胞系(MDA-MB-231和MCF-7)之间的RUVBL1表达水平。利用划痕实验、细胞计数试剂盒-8和Transwell实验评估RUVBL1敲低对BRCA细胞增殖、迁移和侵袭的影响。在RUVBL1表达下调后,进行蛋白质印迹分析和RT-qPCR以研究其在调节β-连环蛋白/LEF-1途径中的作用。上述实验证明,RUVBL1表达的敲低抑制了BRCA细胞的增殖、迁移和侵袭能力,调节了β-连环蛋白/LEF-1途径。总的来说,本研究结果初步证实RUVBL1参与了β-连环蛋白信号通路的分子机制,这可能为BRCA治疗提供一个新的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91e7/11667213/26fd2f9b0316/or-53-02-08855-g00.jpg

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