Department of Oncology, Shanghai Fourth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Oncology, Tianyou Hospital, Tongji University School of Medicine, Shanghai, China.
J Gene Med. 2024 Jan;26(1):e3661. doi: 10.1002/jgm.3661.
Upregulation of SMC1A (Structural maintenance of chromosomes 1A) is linked with many types of cancer and its oncogenic function, which has been associated with crucial cellular mechanisms (cell division, cell cycle checkpoints regulation and DNA repair). Recent studies have shown that SMC1A was involved in breast cancer, although the exact mechanisms of SMC1A remain to be determined.
Using The Cancer Genome Atlas (TCGA) database, we examined SMC1A expression and its relation to other genes, including FOXM1 and STMN1. Short hairpin RNA was used to subsequently examine the biological roles of SMC1A in MDA-MB-231 and MDA-MB-468 cell lines. Bioinformatics were performed to identify the SMC1A-related gene FOXM1.
Here, we used the TCGA database to show that SMC1A is overexpressed in breast cancer. Later investigations showed SMC1A's role in breast cancer cell survival, apoptosis and invasion. Using bioinformatics and western blot assays, we confirmed that FOXM1 acted as the downstream of SMC1A, and SMC1A knockdown significantly downregulated the FOXM1 expression via the AKT signal pathway. Interestingly, the inhibition effects induced by SMC1A downregulation could be reversed by FOXM1 overexpression. In the clinic, SMC1A expression is favorably linked with FOXM1 expression in breast cancer tumor tissues.
Collectively, our results not only enhance our knowledge of SMC1A's molecular pathways in breast cancer, but also suggest a potential new therapeutic target.
SMC1A（染色体 1A 的结构维持）的上调与多种癌症有关，其致癌功能与关键的细胞机制（细胞分裂、细胞周期检查点调节和 DNA 修复）有关。最近的研究表明，SMC1A 参与了乳腺癌，尽管 SMC1A 的确切机制仍有待确定。
我们使用癌症基因组图谱（TCGA）数据库，检查了 SMC1A 的表达及其与其他基因（包括 FOXM1 和 STMN1）的关系。随后使用短发夹 RNA 检查 SMC1A 在 MDA-MB-231 和 MDA-MB-468 细胞系中的生物学作用。进行生物信息学分析以鉴定 SMC1A 相关基因 FOXM1。
在这里，我们使用 TCGA 数据库表明 SMC1A 在乳腺癌中过表达。后来的研究表明 SMC1A 在乳腺癌细胞存活、凋亡和侵袭中的作用。通过生物信息学和 Western blot 分析，我们证实 FOXM1 作为 SMC1A 的下游因子，SMC1A 敲低通过 AKT 信号通路显著下调 FOXM1 的表达。有趣的是，SMC1A 下调引起的抑制作用可以通过 FOXM1 的过表达逆转。在临床上，SMC1A 的表达与乳腺癌肿瘤组织中 FOXM1 的表达呈正相关。
总之，我们的研究结果不仅增强了我们对 SMC1A 在乳腺癌中分子途径的认识，还为潜在的新治疗靶点提供了依据。
