Objective

To explore the mechanism of steroidogenic acute regulatory (StAR)-related lipid transfer domain containing 3 (STARD3) in breast cancer (BC).

Methods

We analysed the differential mRNA expressions of BC using ER⁺and ER^-BC expression profiles from the cancer genome atlas (TCGA). Expression and correlation between salient genes was visualized using microarray volcano plots and a protein–protein interaction (PPI) network map. Survival analyses were performed to identify the potential for STARD3 to serve as a prognostic biomarker. The expression of STARD3 was examined by immunohistochemistry (IHC). The effects of STARD3 on apoptosis and proliferation of BC (MCF-7) cell line were deduced by flow cytometry, CCK8, and western blot (WB).

Results

STARD3 was the most differentially expressed gene (DEG). Patients in the STARD3 high expression group had significantly lower survival than those in the low expression group. The expression of STARD3 was significantly higher in BC tissues than controls. Inhibiting STARD3 expression significantly increased apoptosis, decreased proliferation, activated PI3K/AKT/mTOR pathway

Conclusion

Inhibiting the expression of STARD3 induced apoptosis via the inactivation of PI3K/AKT/mTOR pathway on BC inhibits tumour growth, which can be an effective therapeutic strategy.

中文翻译：

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通过失活PI3K/AKT/mTOR通路抑制STARD3诱导的ER+乳腺癌细胞凋亡

客观的

探讨类固醇急性调节（StAR）相关脂质转移结构域（STARD3）在乳腺癌（BC）中的作用机制。

方法

我们使用来自癌症基因组图谱 (TCGA) 的ER ⁺和 ER ^- BC 表达谱分析了 BC 的差异 mRNA 表达。使用微阵列火山图和蛋白质 - 蛋白质相互作用（PPI）网络图可视化显着基因之间的表达和相关性。进行生存分析以确定 STARD3 作为预后生物标志物的潜力。通过免疫组织化学（IHC）检查STARD3的表达。通过流式细胞术、CCK8和蛋白质印迹（WB）推断STARD3对BC（MCF-7）细胞系凋亡和增殖的影响。

结果

STARD3是最差异表达的基因（DEG）。STARD3高表达组患者的生存率明显低于低表达组患者。BC 组织中 STARD3 的表达显着高于对照组。抑制 STARD3 表达显着增加细胞凋亡，减少增殖，激活 PI3K/AKT/mTOR 通路

结论

通过失活 BC 上的 PI3K/AKT/mTOR 通路来抑制 STARD3 诱导的细胞凋亡的表达，从而抑制肿瘤生长，这可能是一种有效的治疗策略。