miR-539 inhibits FSCN1 expression and suppresses hepatocellular carcinoma migration and invasion.
miR-539 inhibits FSCN1 expression and suppresses hepatocellular carcinoma migration and invasion.
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miR-539 抑制 FSCN1 表达并抑制肝细胞癌迁移和侵袭。
DOI：
10.3892/or.2017.5549
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发表时间：
2017-05
期刊：
影响因子：
4.2
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Liu Y;Hong W;Zhou C;Jiang Z;Wang G;Wei G;Li X
越来越多的证据表明，作为肿瘤抑制因子或癌基因的miRNAs的失调参与了肿瘤的发生。然而，miR-539在肝细胞癌（HCC）中的作用尚未得到充分研究。进行定量RT-PCR（qRT-PCR）、增殖测定、集落形成测定、迁移和侵袭测定、蛋白质印迹和异种移植肿瘤生长模型以评估miR-539在HCC中的表达水平和功能。使用荧光素酶报告基因测定、qRT-PCR、蛋白质印迹和免疫组织化学来鉴定和验证miR-539的靶标。miR-539在HCC细胞系和组织样品中显著下调。miR-539的异位表达在体外抑制细胞活力、增殖、迁移和侵袭，并在体内抑制异种移植肿瘤生长。Fascin homologue 1（FSCN 1）被证实是miR-539的直接靶点，并且FSCN 1的过表达促进HCC细胞的迁移和侵袭。miR-539通过靶向FSCN 1在HCC的发生和发展中发挥新的肿瘤抑制作用，为HCC的发生机制提供了新的见解，并提示miR-539可能是治疗靶点。
Increasing evidence indicates that the dysregulation of miRNAs that act as tumor suppressors or oncogenes is involved in tumorigenesis. However, the role of miR-539 in hepatocellular carcinoma (HCC) has not been well investigated. Quantitative RT-PCR (qRT-PCR), proliferation assay, colony formation assay, migration and invasion assays, western blotting, and xenograft tumor growth models were performed to assess the expression levels and functions of miR-539 in HCC. Luciferase reporter assays, qRT-PCR, western blotting, and immunohistochemistry were used to identify and verify the targets of miR-539. miR-539 was significantly downregulated in HCC cell lines and tissue samples. Ectopic expression of miR-539 inhibited cell viability, proliferation, migration, and invasion in vitro and suppressed xenograft tumor growth in vivo. Fascin homologue 1 (FSCN1) was verified as a direct target of miR-539, and overexpression of FSCN1 promoted HCC cell migration and invasion. miR-539 acts as a novel tumor suppressor in the development and progression of HCC by targeting FSCN1, providing new insight into the mechanisms of HCC carcinogenesis and suggesting that miR-539 may be a therapeutic target.