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外泌体 miR-93 通过直接抑制 TIMP2/TP53INP1/CDKN1A 促进肝癌细胞的增殖和侵袭。

Exosomal miR-93 promotes proliferation and invasion in hepatocellular carcinoma by directly inhibiting TIMP2/TP53INP1/CDKN1A.

机构信息

Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.

Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.

出版信息

Biochem Biophys Res Commun. 2018 Aug 25;502(4):515-521. doi: 10.1016/j.bbrc.2018.05.208. Epub 2018 Jun 4.

Abstract

Hepatocellular carcinoma (HCC) is a malignant cancer worldwide; lacking biomarkers for early prognostication contributes to its high lethality. Herein, we report a novel biomarker, exosome delivered miR-93, is up-regulated in HCC cell line media and serum samples of HCC patients. We measured the proliferation and invasion ability of HCC cell lines following exosomal miR-93 treatment. After prediction with online algorithms, we further confirmed that TP53INP1, TIMP2 and CDKN1A are direct targets of miR-93 by dual-luciferase reporter assay. In addition, the diagnostic value of exosomal miR-93 was evaluated by qPCR and ROC analysis. The significant correlation between serum exosomal miR-93 and clinical information including stage, tumor size were observed. Furthermore, the survival differences of HCC patients with high or low miR-93 were statistically significant using Kaplan-Meier analysis. In summary, our work identified exosomal miR-93 as a novel biomarker for both diagnosis and prognosis in HCC.

摘要

肝细胞癌 (HCC) 是一种全球性的恶性肿瘤;缺乏早期预后的生物标志物导致其高致死率。在此,我们报告了一种新型生物标志物,外泌体递送的 miR-93,在 HCC 细胞系培养基和 HCC 患者血清样本中上调。我们测量了外泌体 miR-93 处理后 HCC 细胞系的增殖和侵袭能力。通过在线算法预测后,我们通过双荧光素酶报告实验进一步证实 TP53INP1、TIMP2 和 CDKN1A 是 miR-93 的直接靶标。此外,通过 qPCR 和 ROC 分析评估了外泌体 miR-93 的诊断价值。观察到血清外泌体 miR-93 与包括分期、肿瘤大小在内的临床信息之间存在显著相关性。此外,Kaplan-Meier 分析显示,miR-93 高或低的 HCC 患者的生存差异具有统计学意义。总之,我们的工作确定了外泌体 miR-93 是 HCC 诊断和预后的新型生物标志物。

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