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抑制 STARD3 的表达通过灭活 PI3K/AKT/mTOR 通路诱导 ER 乳腺癌细胞凋亡。

Inhibiting the expression of STARD3 induced apoptosis via the inactivation of PI3K/AKT/mTOR pathway on ER breast cancer.

机构信息

Department of Pathology, Wuxi No. 2 People's Hospital, Affiliated Wuxi Clinical College of Nantong University, Wuxi, Jiangsu Province 214002, PR China; Department of Pathology, Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University, Wuxi 214002, PR China.

Translational Medical Research Centre, Wuxi No. 2 People's Hospital, Affiliated Wuxi Clinical College of Nantong University, Wuxi, Jiangsu Province 214002, PR China; Translational Medical Research Centre, Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University, Wuxi 214002, PR China.

出版信息

Tissue Cell. 2022 Dec;79:101971. doi: 10.1016/j.tice.2022.101971. Epub 2022 Oct 31.

DOI:10.1016/j.tice.2022.101971
PMID:36375355
Abstract

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 ERand ERBC 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.

摘要

目的

探索类固醇急性调节蛋白(StAR)相关脂质转移结构域包含蛋白 3(STARD3)在乳腺癌(BC)中的作用机制。

方法

我们使用癌症基因组图谱(TCGA)中的 ER 和 ERBC 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 Western blot(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。与对照相比,BC 组织中 STARD3 的表达明显升高。抑制 STARD3 表达显着增加凋亡,减少增殖,激活 PI3K/AKT/mTOR 通路。

结论

抑制 STARD3 的表达通过失活 PI3K/AKT/mTOR 通路诱导 BC 中的细胞凋亡抑制肿瘤生长,这可能是一种有效的治疗策略。

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