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下调 microRNA-196a 通过靶向 FOXO1 抑制人肝癌细胞的增殖和侵袭。

Downregulation of microRNA-196a inhibits human liver cancer cell proliferation and invasion by targeting FOXO1.

机构信息

Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, P.R. China.

Department of Surgery, Jingan Branch of Huashan Hospital, Fudan University, Shanghai, P.R. China.

出版信息

Oncol Rep. 2017 Oct;38(4):2148-2154. doi: 10.3892/or.2017.5873. Epub 2017 Aug 3.

Abstract

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and effective therapy for human liver cancer remains a difficult clinical concern. Researchers have demonstrated that microRNAs play important roles in the tumorigenesis and tumor progression of human liver cancer; therefore, regulation of microRNAs may be a new strategy for HCC therapy. MicroRNA-196a (miR-196a) has been reported to be overexpressed in many types of cancers. However, the regulatory effects of miR-196a in human liver cancer are not fully understood. In the present study, we found that miR-196a was overexpressed in human liver cancer cells compared to that observed in normal liver cells. MTT and colony formation assays indicated that downregulation of miR-196a inhibited liver cancer cell proliferation which was due to the induction of cell apoptosis. A mouse model demonstrated that downregulation of miR-196a also inhibited human liver cancer cell migration and invasion in vivo. Further study indicated that FOXO1 is a direct target of miR-196a, and inhibition of FOXO1 promoted human liver cancer cell growth. Taken together, the present study demonstrated that the expression of miR-196a in human liver cancer cells was upregulated; downregulation of miR-196a regulated human liver cancer cell biological functions which could benefit the clinical therapy of human liver cancer in the future.

摘要

肝细胞癌(HCC)是成人原发性肝癌中最常见的类型,有效的肝癌治疗仍然是一个临床难题。研究人员已经证明,microRNAs 在人类肝癌的肿瘤发生和肿瘤进展中发挥重要作用;因此,microRNAs 的调控可能是 HCC 治疗的一种新策略。microRNA-196a(miR-196a)在许多类型的癌症中表达过度。然而,miR-196a 对人类肝癌的调控作用尚不完全清楚。在本研究中,我们发现 miR-196a 在肝癌细胞中表达过度,而在正常肝细胞中则观察到 miR-196a 的表达。MTT 和集落形成实验表明,下调 miR-196a 抑制肝癌细胞增殖,这是由于细胞凋亡的诱导。小鼠模型表明,下调 miR-196a 也抑制了体内人肝癌细胞的迁移和侵袭。进一步的研究表明,FOXO1 是 miR-196a 的直接靶标,抑制 FOXO1 促进了人肝癌细胞的生长。综上所述,本研究表明,miR-196a 在人肝癌细胞中的表达上调;下调 miR-196a 调节人肝癌细胞的生物学功能,这可能有益于未来人类肝癌的临床治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9af/5652959/16f561955cab/OR-38-04-2148-g00.jpg

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