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抑制整合素β1/AKT信号通路可抑制卵巢癌进展。

The Overexpression of Suppresses the Ovarian Cancer Progression the Inhibition of Integrin β1/AKT Signaling Pathway.

作者信息

Yan Limei, He Zeping, Li Wei, Liu Ning, Gao Song

机构信息

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.

出版信息

Front Oncol. 2021 Mar 31;11:644840. doi: 10.3389/fonc.2021.644840. eCollection 2021.

Abstract

Ovarian cancer is considered as one of the most fatal gynecologic malignancies. This work aimed to explore the effects and regulatory mechanism of (, a subunit of CoA ligases) in ovarian cancer progression. As well as employing CCK-8 assay, clone formation assay, and cell cycle analysis were carried out to investigate cell proliferation ability. Wound healing assay and transwell assay were subsequently used to assess cell migration and invasion. Mice xenografts were then conducted to measure the effects of on tumor development . Our bioinformatics analysis suggested that the expression of was down-regulated in ovarian cancer tissues, and the low expression level of might related with poorer overall survival than high mRNA expression of in ovarian cancer patients. We artificially regulated the expression of to evaluate its effects on ovarian cancer malignant phenotypes. Our data revealed that the overexpression of inhibited cell proliferation, migration, and invasion of ovarian cancer cells. In contrast, the knock-down of received the opposite results. Our western blot results showed that the Integrin β1/AKT signaling pathway was negatively regulated by expression. Moreover, overexpression-induced suppression of cell migration and invasion activities were abolished by the overexpression of (Integrin β1). Additionally, the growth of ovarian cancer xenograft tumors was also repressed by the overexpression of . And interference obtained the contrary effects . In summary, acts as a tumor suppressor gene and may be a potential therapeutic target of ovarian cancer.

摘要

卵巢癌被认为是最致命的妇科恶性肿瘤之一。这项研究旨在探讨辅酶A连接酶的一个亚基( )在卵巢癌进展中的作用及调控机制。同时采用CCK-8法、克隆形成试验和细胞周期分析来研究细胞增殖能力。随后使用伤口愈合试验和Transwell试验评估细胞迁移和侵袭能力。接着进行小鼠异种移植实验以检测 对肿瘤发展的影响。我们的生物信息学分析表明, 在卵巢癌组织中的表达下调,并且在卵巢癌患者中, 低表达水平可能与总体生存率较差有关,而 高mRNA表达则相反。我们人工调节 的表达以评估其对卵巢癌恶性表型的影响。我们的数据显示, 的过表达抑制了卵巢癌细胞的增殖、迁移和侵袭。相反,敲低 则得到相反的结果。我们的蛋白质印迹结果表明,整合素β1/AKT信号通路受到 表达的负调控。此外, 的过表达诱导的细胞迁移和侵袭活性抑制被整合素β1( )的过表达所消除。另外, 的过表达也抑制了卵巢癌异种移植肿瘤的生长。而干扰 则产生相反的效果。总之, 作为一种肿瘤抑制基因,可能是卵巢癌潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1395/8045751/60356518bdd0/fonc-11-644840-g001.jpg

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