文章：

RSRC2表达通过转录调控SCIN表达抑制三阴性乳腺癌恶性进展

RSRC2 Expression Inhibits Malignant Progression of Triple-Negative Breast Cancer by Transcriptionally Regulating SCIN Expression

原文发布日期：19 December 2023

DOI: 10.3390/cancers16010015

类型: Article

开放获取: 是

英文摘要：

Triple-negative breast cancer (TNBC) has a shorter survival time and higher mortality rate than other molecular subtypes. RSRC2 is a newly discovered tumor suppressor gene. However, the potential functional mechanism of RSRC2 in TNBC remains unknown so far. Multiple bioinformatics databases were used. A Human Transcriptome Array 2.0 analysis, ChIP-seq analysis, ChIP-qPCR, RT-qPCR, Western blot, cell function assays in vitro and a metastatic mouse model in vivo were performed to demonstrate the role of RSRC2 in TNBC. Through the analysis of various databases, RSRC2 expression was the lowest in TNBC tissues compared to other molecular subtypes. The low expression of RSRC2 was associated with a worse prognosis for patients with breast cancer. The transcriptome array, ChIP-seq and bioinformatics analysis identified that GRHL2 and SCIN might have a close relationship with RSRC2. The functional bioinformatics enrichment analysis and functional cell experiments showed that RSRC2 was involved in cell adhesion, cell proliferation, cell migration and invasion. Furthermore, RSRC2 expression suppressed SCIN expression but not GRHL2 expression. SCIN re-expression in the RSRC2 overexpression cells or SCIN knockdown in the RSRC2 knockdown cells reversed the cellular function caused by RSRC2. Mechanistically, RSRC2 transcriptionally inhibited SCIN expression. In summary, our study reveals that RSRC2 acts as a tumor suppressor in TNBC development and progression through negatively regulating SCIN-mediated cell function, thus providing a potential target for TNBC treatment.

摘要翻译： 

与其他分子亚型相比，三阴性乳腺癌（TNBC）具有更短的生存时间和更高的死亡率。RSRC2是一种新发现的抑癌基因，但其在TNBC中的潜在功能机制目前尚不清楚。本研究综合运用多种生物信息学数据库进行分析，并采用人类转录组芯片2.0分析、染色质免疫沉淀测序、染色质免疫沉淀定量聚合酶链反应、实时定量聚合酶链反应、蛋白质印迹法、体外细胞功能实验以及体内转移小鼠模型等方法，系统阐明了RSRC2在TNBC中的作用机制。通过多数据库分析发现，与其他分子亚型相比，RSRC2在TNBC组织中的表达水平最低，其低表达与乳腺癌患者不良预后显著相关。转录组芯片、染色质免疫沉淀测序及生物信息学分析表明，GRHL2和SCIN可能与RSRC2存在密切关联。功能富集分析和细胞实验证实，RSRC2参与调控细胞黏附、增殖、迁移和侵袭过程。进一步研究发现，RSRC2过表达可抑制SCIN表达，但对GRHL2表达无显著影响。在RSRC2过表达细胞中重新表达SCIN，或在RSRC2敲低细胞中敲低SCIN，均可逆转由RSRC2调控的细胞功能。机制研究表明，RSRC2通过转录调控抑制SCIN表达。综上所述，本研究发现RSRC2通过负向调控SCIN介导的细胞功能，在TNBC发生发展中发挥抑癌作用，这为TNBC治疗提供了潜在靶点。

原文链接：

RSRC2 Expression Inhibits Malignant Progression of Triple-Negative Breast Cancer by Transcriptionally Regulating SCIN Expression