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蛇床子素通过上调肿瘤抑制因子GNG7抑制乳腺癌进展。

Osthole Inhibits Breast Cancer Progression through Upregulating Tumor Suppressor GNG7.

作者信息

Mei Jie, Wang Tiejun, Zhao Shaojie, Zhang Yan

机构信息

Department of Gynecology and Obstetrics, Wuxi Maternal and Child Health Hospital, The Affiliated Hospital to Nanjing Medical University, Wuxi 214000, Jiangsu, China.

Wuxi Clinical Medical College, Nanjing Medical University, Wuxi 214000, Jiangsu, China.

出版信息

J Oncol. 2021 Feb 27;2021:6610511. doi: 10.1155/2021/6610511. eCollection 2021.

Abstract

Osthole (OST) is a plant-derived compound that can inhibit the proliferation of tumor cells and has a tumor-suppressive effect in multiple types of cancers. However, the mechanisms of OST-mediated breast cancer (BrCa) inhibition were still largely unknown. In this study, we made full use of the GSE85871 dataset to identify potential targets of OST in BrCa multiple bioinformatics analysis. Next, a series of experiments were conducted to check the role of GNG7 in BrCa and the relationship between OST and GNG7. Through a series of bioinformatics analyses, GNG7 was identified as a potential target of OST, which could be significant upregulated by OST exposure in BrCa cells. Besides, GNG7 was lowly expressed in BrCa tissues compared with normal breast tissues, and BrCa patients with low GNG7 expression had shorter overall survival (OS) and relapse-free survival (RFS) compared with those with high GNG7 expression. Moreover, GNG7 silencing significantly enhanced cell proliferation and inhibited apoptosis, and exogenous overexpression of GNG7 showed reverse effects on BrCa cells. Last but not least, GNG7 inhibition could notably rescue OST-mediated cytotoxic effects. In summary, we identified GNG7 as a novel target for OST in BrCa and a potential tumor suppressor. Thus, OST could be therapeutically beneficial for BrCa through a GNG7-dependent mechanism.

摘要

蛇床子素(OST)是一种植物源化合物,能够抑制肿瘤细胞增殖,对多种癌症具有肿瘤抑制作用。然而,OST介导的乳腺癌(BrCa)抑制机制仍不清楚。在本研究中,我们充分利用GSE85871数据集,通过多种生物信息学分析来确定OST在BrCa中的潜在靶点。接下来,进行了一系列实验以检测GNG7在BrCa中的作用以及OST与GNG7之间的关系。通过一系列生物信息学分析,GNG7被确定为OST的潜在靶点,在BrCa细胞中,OST处理可使其显著上调。此外,与正常乳腺组织相比,GNG7在BrCa组织中低表达,GNG7低表达的BrCa患者与高表达患者相比,总生存期(OS)和无复发生存期(RFS)更短。而且,沉默GNG7可显著增强细胞增殖并抑制细胞凋亡,而外源性过表达GNG7对BrCa细胞具有相反作用。最后,抑制GNG7可显著挽救OST介导的细胞毒性作用。总之,我们确定GNG7是BrCa中OST的新靶点和潜在的肿瘤抑制因子。因此,OST可能通过依赖GNG7的机制对BrCa治疗有益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53b8/7937475/b819087aede4/JO2021-6610511.001.jpg

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