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miR-494-3p 通过靶向 PTEN 促进 PI3K/AKT 通路过度激活和人肝癌进展。

MiR-494-3p promotes PI3K/AKT pathway hyperactivation and human hepatocellular carcinoma progression by targeting PTEN.

机构信息

The First Department of General Surgeny, Shidong Hospital, Yangpu District, Shanghai, Anhui Medical University, 999 Shiguang Road, Shanghai, 200438, China.

The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200438, China.

出版信息

Sci Rep. 2018 Jul 11;8(1):10461. doi: 10.1038/s41598-018-28519-2.

Abstract

Recent studies have shown that miR-494-3p is oncogene and has a central role in many solid tumors; however, the role of miR-494-3p in the progression and prognosis of hepatocellular carcinoma (HCC) remains unknown. In this study, it was found that miR-494-3p was up-regulated in HCC tissues. The high level of miR-494-3p in HCC tumors was correlated with aggressive clinicopathological characteristics and predicted poor prognosis in HCC patients. Functional study demonstrated that miR-494-3p significantly promoted HCC cell metastasis in vitro and vivo. Since phosphoinositide 3-kinase/protein kinase-B (PI3K/AKT) signaling is a basic oncogenic driver in HCC, a potential role of miR-494-3p was explored as well as its target genes in PI3K/AKT activation. Of all the predicted target genes of miR-494-3p, the tumor-suppressor phosphatase and tensin homolog (PTEN) were identified. In conclusion, the data we collected could define an original mechanism of PI3K/AKT hyperactivation and sketch the regulatory role of miR-494-3p in suppressing the expression of PTEN. Therefore, targeting miR-494-3p could provide an effective therapeutic method for the treatment of the disease.

摘要

最近的研究表明,miR-494-3p 是一种癌基因,在许多实体肿瘤中具有核心作用;然而,miR-494-3p 在肝细胞癌(HCC)进展和预后中的作用尚不清楚。在这项研究中,发现 miR-494-3p 在 HCC 组织中上调。HCC 肿瘤中 miR-494-3p 的高水平与侵袭性临床病理特征相关,并预测 HCC 患者的预后不良。功能研究表明,miR-494-3p 显著促进 HCC 细胞在体外和体内的转移。由于磷酸肌醇 3-激酶/蛋白激酶 B(PI3K/AKT)信号通路是 HCC 中的基本致癌驱动因素,因此也探索了 miR-494-3p 及其在 PI3K/AKT 激活中的靶基因的潜在作用。在 miR-494-3p 的所有预测靶基因中,鉴定出肿瘤抑制因子磷酸酶和张力蛋白同源物(PTEN)。总之,我们收集的数据可以定义 PI3K/AKT 过度激活的原始机制,并描绘 miR-494-3p 抑制 PTEN 表达的调节作用。因此,针对 miR-494-3p 可能为该疾病的治疗提供一种有效的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c24/6041272/508cada99ca1/41598_2018_28519_Fig1_HTML.jpg

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