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UHRF1 受 miR-124-3p 调控并促进肝内胆管癌细胞增殖。

UHRF1 is regulated by miR-124-3p and promotes cell proliferation in intrahepatic cholangiocarcinoma.

机构信息

Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Ministry of Education, Shanghai, China.

出版信息

J Cell Physiol. 2019 Nov;234(11):19875-19885. doi: 10.1002/jcp.28586. Epub 2019 Apr 15.

Abstract

Ubiquitin-like with PHD and ring finger domains 1 (UHRF1) is abnormally overexpressed in multiple cancers and closely correlated with tumor-promoting effects, such as high proliferation. However, how UHRF1 functions in intrahepatic cholangiocarcinoma (ICC) has not yet been determined. Herein, we found that UHRF1 is overexpressed in ICC tissues. Downregulated UHRF1 attenuated the transition of the G1/S cell cycle and then suppressed cell proliferation in vitro and tumor growth in vivo. Moreover, upstream regulators of the UHRF1 expression were predicted, and we found that direct binding of miR-124-3p inhibited the UHRF1 expression. Elevated miR-124-3p suppressed proliferation and led to the arrest of the cell cycle. Furthermore, the expression of UHRF1 was positively correlated with PCNA. Clinically, we showed that elevated UHRF1 was associated with poor prognosis, and served as an independent prognostic factor in ICC patients. Together, these findings demonstrate that UHRF1, regulated by miR-124-3p, acts as a tumor promoter by promoting cell proliferation in ICC.

摘要

泛素样含 PHF 和环指结构域蛋白 1(UHRF1)在多种癌症中异常过表达,与促进肿瘤的作用密切相关,如高增殖。然而,UHRF1 在肝内胆管癌(ICC)中的作用尚不清楚。在此,我们发现 UHRF1 在 ICC 组织中过表达。下调 UHRF1 减弱了 G1/S 细胞周期的转变,从而抑制了体外细胞增殖和体内肿瘤生长。此外,预测了 UHRF1 表达的上游调节剂,我们发现 miR-124-3p 的直接结合抑制了 UHRF1 的表达。升高的 miR-124-3p 抑制增殖并导致细胞周期停滞。此外,UHRF1 的表达与 PCNA 呈正相关。临床上,我们表明,UHRF1 的升高与预后不良相关,是 ICC 患者的独立预后因素。综上所述,这些发现表明,受 miR-124-3p 调控的 UHRF1 通过促进 ICC 中的细胞增殖来发挥肿瘤促进作用。

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