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CIP2A,一种癌蛋白,与喉癌细胞的增殖、侵袭和迁移有关。

CIP2A, an oncoprotein, is associated with cell proliferation, invasion and migration in laryngeal carcinoma cells.

机构信息

Department of Otolaryngology, First Hospital of Ningbo City, Ningbo City, Zhejiang 315000, P.R. China.

出版信息

Oncol Rep. 2017 Aug;38(2):1005-1012. doi: 10.3892/or.2017.5759. Epub 2017 Jun 27.

Abstract

Laryngeal carcinoma is one of the most common malignant tumors in otorhinolaryngology. Moreover, experimental investigation showed that cancerous inhibitor of protein phosphatase 2A (CIP2A) expressed highly in various cancers. Therefore, we investigated whether CIP2A can regulate the proliferation, invasion and migration by RNA interference in Hep-2 cells and AMC-NH-8 cells and further affect the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway. Overexpression of CIP2A was evaluated in tumor tissue and laryngeal cancer cell lines (Hep-2 and AMC-NH-8 cells) by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot assay. In a follow-up experiment, we confirmed that CIP2A siRNA effectively suppressed the cell proliferation at 48 and 72 h, and arrested cell cycle at G0/G1 in Hep-2 cells and AMC-NH-8 cells. The invasion and migration of cell in siRNA CIP2A group were markedly inhibited. Moreover, the experimental results showed that the expression levels of invasion- and migration-related genes, including E-cadherin, metastasis-associated gene 1 (MTA1) and matrix metalloproteinases-2/9 (MMP-2/9), were regulated by CIP2A siRNA. Phosphorylation levels of PI3K and AKT proteins were reduced by CIP2A siRNA. Importantly, it suggested signaling through PI3K/Akt as a critical mechanism by which CIP2A siRNA may suppress cell proliferation, invasion and migration in laryngeal carcinoma cells.

摘要

喉癌是耳鼻喉科最常见的恶性肿瘤之一。此外,实验研究表明,蛋白磷酸酶 2A 的致癌抑制剂(CIP2A)在各种癌症中表达水平较高。因此,我们通过 RNA 干扰研究了 CIP2A 是否可以调节 Hep-2 细胞和 AMC-NH-8 细胞的增殖、侵袭和迁移,并进一步影响磷脂酰肌醇 3-激酶(PI3K)/蛋白激酶 B(AKT)通路的激活。通过实时定量聚合酶链反应(RT-qPCR)和 Western blot 检测,评估 CIP2A 在肿瘤组织和喉癌细胞系(Hep-2 和 AMC-NH-8 细胞)中的表达。在后续实验中,我们证实 CIP2A siRNA 可有效抑制 Hep-2 细胞和 AMC-NH-8 细胞在 48 和 72 小时的细胞增殖,并将细胞周期阻滞在 G0/G1 期。siRNA CIP2A 组的细胞侵袭和迁移明显受到抑制。此外,实验结果表明,侵袭和迁移相关基因的表达水平,包括 E-钙黏蛋白、转移相关基因 1(MTA1)和基质金属蛋白酶-2/9(MMP-2/9),受 CIP2A siRNA 调节。CIP2A siRNA 降低了 PI3K 和 AKT 蛋白的磷酸化水平。重要的是,研究表明,PI3K/Akt 信号通路是 CIP2A siRNA 抑制喉癌细胞增殖、侵袭和迁移的关键机制之一。

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