将代谢蛋白ATP5MF鉴定为TNBC的潜在治疗靶点

三阴性乳腺癌（TNBC）是一种独特的乳腺癌亚型，其特征是其侵入性高，转移性高，复发性的倾向和预后不良。非BRCA1/2突变TNBC的有效治疗方案仍然缺乏。结果，存在针对非BRCA1/2突变TNBC开发新型治疗方法的紧迫临床必要性。对于这项研究，SCRNA数据是从GEO数据库中获得的，而转录组数据是从TCGA和Anbabric数据库中获得的。在单细胞测序数据上进行了质量控制程序。然后将注释和模仿算法用于厌食。采用高维加权基因共表达网络分析（HDWGCNA）方法，我们分析了非BRCA1/2突变TNBC的肿瘤上皮细胞，以识别功能模块基因。 PPI分析和生存分析进一步促进了关键基因。将siRNA-NC和siRNA-ATP5MF转染到两个MDA-MB-231和BT-549 TNBC细胞系中。通过CCK8分析，菌落形成和迁移测定法确定细胞生长。电子显微镜用于检查细胞中线粒体的结构。 JC-1染色用于测量线粒体膜的电势。通过将TNBC细胞注入裸鼠，建立了肿瘤异种移植模型。在ATP5MF沉默后，该动物模型用于评估体内肿瘤反应。使用HDWGCNA，我们在模块3中鉴定了136个基因。PPI和生存分析后，我们已经将ATP5MF确定为潜在的治疗基因。高ATP5MF表达与非BRCA1/2突变TNBC的预后不良有关。使用临床TNBC标本的TCGA数据库和IHC染色评估了TNBC组织中ATP5MF的高表达。在两种TNBC细胞系中将ATP5MF沉默，从而降低了TNBC细胞体外的生长和落形成，并阻碍了体内TNBC异种移植物的生长。此外，tNBC细胞中的线粒体功能受损的ATP5MF敲低。总而言之，代谢蛋白ATP5MF在非BRCA1/2突变TNBC细胞中起着至关重要的作用，使其成为非BRCA1/2突变的潜在新型诊断和治疗性Oncotarget tnbc。

Triple-negative breast cancer (TNBC), a distinct subtype of breast cancer, is characterized by its high invasiveness, high metastatic potential, proneness to relapse, and poor prognosis. Effective treatment regimens for non-BRCA1/2 mutation TNBC are still lacking. As a result, there is a pressing clinical necessity to develop novel treatment approaches for non-BRCA1/2 mutation TNBC.For this research, the scRNA data was obtained from the GEO database, while the transcriptome data was obtained from the TCGA and METABRIC databases. Quality control procedures were conducted on single-cell sequencing data. and then annotation and the Copycat algorithm were applied for anlysis. Employing the high dimensional weighted gene coexpression network analysis (hdWGCNA) method, we analyzed the tumor epithelial cells from non-BRCA1/2 mutation TNBC to identify the functional module genes. PPI analysis and survival analysis were further emplyed to identify the key gene. siRNA-NC and siRNA-ATP5MF were transfected into two MDA-MB-231 and BT-549 TNBC cell lines. Cell growth was determined by CCK8 assay, colony formation and migration assay. Electron microscopy was used to examine the structure of mitochondria in cells. JC-1 staining was used to measure the potential of the mitochondrial membrane. A tumor xenograft animal model was established by injecting TNBC cells into nude mice. The animal model was usded to evaluated in vivo tumor response aftering ATP5MF silencing.Using hdWGCNA, we have identified 136 genes in module 3. After PPI and survival analysis, we have identified ATP5MF as a potential therapeutic gene. High ATP5MF expression was associated with poor prognosis of non-BRCA1/2 mutation TNBC. The high expression of ATP5MF in TNBC tissues was evaluated using the TCGA database and IHC staining of clinical TNBC specimens. Silencing ATP5MF in two TNBC cell lines reduced the growth and colony formation of TNBC cells in vitro, and hindered the growth of TNBC xenografts in vivo. Additionally, ATP5MF knockdown impaired mitochondrial functions in TNBC cells.In summary, the metabolic protein ATP5MF plays a crucial role in the non-BRCA1/2 mutation TNBC cells, making it a potential novel diagnostic and therapeutic oncotarget for non-BRCA1/2 mutation TNBC.