Department of Clinical Laboratory, Women and Children's Hospital of Chongqing Medical University, Chongqing, 401174, China.
Department of Clinical Laboratory, Chongqing Health Center for Women and Children, Chongqing, 401174, China.
Sci Rep. 2024 Sep 19;14(1):21914. doi: 10.1038/s41598-024-72562-1.
SASH1 (SAM and SH3 domain containing 1) has been increasingly reported as a tumor suppressor gene. However, there is limited research on the role of SASH1 in breast cancer. This manuscript aims to investigate the mechanism of SASH1 in the occurrence, development, and prognosis of breast cancer. Firstly, we obtained RNA-sequencing data of the tumors from the Genomic Data Commons data portal website, along with the corresponding clinical information of patients. Pan-cancer analysis was performed to analyze the expression of SASH1 across all tumors. Univariate Cox regression analysis was used to assess the correlation between SASH1 expression and the prognosis of breast cancer patients. Then, immunohistochemistry was utilized to evaluate the expression levels of SASH1, p-Akt, p-PI3K, and p-mTOR in breast cancer tissue. Finally, a cell assay was employed to analyze the impact of SASH1 on the proliferation and invasion of breast cancer cells (MDA-MB-231). The results revealed that SASH1 expression is decreased in BRCA, LUSC, LUAD, CESC, ESCA, and COAD. Meta-analysis also found that SASH1 is downregulated in most tumor tissues, and the expression level of SASH1 in breast cancer was significantly lower than that in the control group (OR = 0.14, 95% CI = 0.08-0.25; P < 0.001). Further experimental validation showed that SASH1 expression is significantly downregulated in breast cancer tissue (38.33%, 23/60), and the overexpression of SASH1 can inhibit the proliferation and invasion of breast cancer cells accompanied by the suppression of PI3K-Akt-mTOR signaling pathway. Additionally, SASH1 overexpression can improve OS and RFS of breast cancer patients.
SASH1（SAM 和 SH3 结构域包含蛋白 1）已被越来越多地报道为肿瘤抑制基因。然而，关于 SASH1 在乳腺癌中的作用的研究有限。本手稿旨在研究 SASH1 在乳腺癌发生、发展和预后中的作用机制。首先，我们从基因组数据共享数据门户网站获得了肿瘤的 RNA-seq 数据，以及患者的相应临床信息。进行泛癌分析以分析所有肿瘤中 SASH1 的表达。使用单变量 Cox 回归分析评估 SASH1 表达与乳腺癌患者预后的相关性。然后，使用免疫组织化学评估 SASH1、p-Akt、p-PI3K 和 p-mTOR 在乳腺癌组织中的表达水平。最后，进行细胞实验分析 SASH1 对乳腺癌细胞（MDA-MB-231）增殖和侵袭的影响。结果表明，SASH1 在 BRCA、LUSC、LUAD、CESC、ESCA 和 COAD 中表达降低。荟萃分析还发现 SASH1 在大多数肿瘤组织中下调，并且乳腺癌中 SASH1 的表达水平明显低于对照组（OR=0.14，95%CI=0.08-0.25；P<0.001）。进一步的实验验证表明 SASH1 在乳腺癌组织中表达显著下调（38.33%，23/60），SASH1 的过表达可以抑制乳腺癌细胞的增殖和侵袭，同时抑制 PI3K-Akt-mTOR 信号通路。此外，SASH1 过表达可以改善乳腺癌患者的 OS 和 RFS。
