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Oct4 促进肝癌细胞增殖和迁移,并通过 survivin/STAT3 通路导致不良预后。

Oct4 promotes cancer cell proliferation and migration and leads to poor prognosis associated with the survivin/STAT3 pathway in hepatocellular carcinoma.

机构信息

Department of Hepatobiliary Surgery, Wujiang No. 1 People's Hospital, Suzhou, Jiangsu 215200, P.R. China.

出版信息

Oncol Rep. 2018 Aug;40(2):979-987. doi: 10.3892/or.2018.6491. Epub 2018 Jun 14.

Abstract

Octamer‑binding transcription factor 4 (Oct4) has been identified as a novel transcription factor associated with tumorigenesis, acquisition and maintenance of cancer stem cell characteristics and poor prognosis in tumors. However, the role of Oct4 in tumorigenesis and progression of hepatocellular carcinoma (HCC) has not yet been fully elucidated. In our present study, we observed that the Oct4 expression level was upregulated in HCC specimens as well as in different HCC cell lines. In in vitro experiments, decreased expression of Oct4 by shRNA inhibited the viability and mobility of HCC cells. Furthermore, the loss of Oct4 inhibited HCC cell malignant progression accompanied by downregulated expression of the survivin/signal transducer and activator of transcription 3 (STAT3) pathway. Liver cancer patients with high expression of Oct4 exhibited significantly shorter overall and disease‑free survival. These findings demonstrated that Oct4 plays a vital role in the malignant progression of HCC cells through the survivin/STAT3 signaling pathway, and it may prove to be a novel biomarker associated with patient prognosis and survival.

摘要

八聚体结合转录因子 4(Oct4)已被鉴定为一种与肿瘤发生、肿瘤干细胞特征的获得和维持以及肿瘤预后不良相关的新型转录因子。然而,Oct4 在肝细胞癌(HCC)发生和进展中的作用尚未完全阐明。在本研究中,我们观察到 Oct4 的表达水平在 HCC 标本以及不同的 HCC 细胞系中上调。在体外实验中,shRNA 下调 Oct4 的表达抑制 HCC 细胞的活力和迁移。此外,Oct4 的缺失抑制了 HCC 细胞的恶性进展,同时下调了生存素/信号转导子和转录激活子 3(STAT3)通路的表达。Oct4 高表达的肝癌患者总生存期和无病生存期明显缩短。这些发现表明,Oct4 通过生存素/STAT3 信号通路在 HCC 细胞的恶性进展中发挥重要作用,它可能成为与患者预后和生存相关的新型生物标志物。

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