MicroRNA-27a-3p inhibits cell viability and migration through down-regulating DUSP16 in hepatocellular carcinoma
MicroRNA-27a-3p inhibits cell viability and migration through down-regulating DUSP16 in hepatocellular carcinoma
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DOI：
10.1002/jcb.26526
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发表时间：
2018-07-01
影响因子：
4
通讯作者：
Ji, Jian-Song
中科院分区：
文献类型：
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作者：
Li, Jin-Mao;Zhou, Jun;Ji, Jian-Song
MicroRNA（miRNA或miR）已被证明在许多不同癌症的发生和发展中起重要作用。在此，我们基于TCGA数据库证明了与邻近正常肝组织相比，miR-27 a-3 p在肝细胞癌（HCC）组织中的表达下调。CCK-8法和流式细胞术检测细胞活力和凋亡。通过Transwell和伤口愈合实验检测细胞的侵袭和迁移。通过荧光素酶测定和蛋白质印迹测定评估miR-27 a-3 p对DUSP 16表达的影响。转染miR-27 a-3 p模拟物上调miR-27 a-3 p表达可明显降低SMMC-7721和HepG 2细胞的存活率、侵袭能力和迁移能力。此外，我们发现双特异性磷酸酶16（DUSP 16），也称为丝裂原活化蛋白激酶磷酸酶7（MKP-7），是miR-27 a-3 p的靶点。miR-27 a-3 p在SMMC-7721和HepG 2细胞中均能显著降低DUSP 16的表达。基于TCGA数据库，DUSP 16在HCC组织中的表达与在邻近肝组织中的表达相比上调。过表达DUSP 16可显著逆转SMMC-7721和HepG 2细胞中miR-27 a-3 p上调导致的细胞活力、侵袭和迁移的变化。我们的发现有助于目前对miR-27 a-3 p功能的理解，并提出了miR-27 a-3 p通过靶向DUSP 16在HCC发展中发挥抗肿瘤作用的机制。
MicroRNA (miRNA or miR) has been shown to play an important role in the initiation and development in many different cancers. Here, we demonstrated down-regulated expression of miR-27a-3p in hepatocellular carcinoma (HCC) tissues in comparison with that in adjacent normal liver tissues based on the TCGA database. Cells viability and apoptosis was measured by CCK-8 and flow cytometry assay. Cell invasion and migration was measured by Transwell and wound healing assay. The effect of miR-27a-3p on DUSP16 expression was evaluated by luciferase assays, and western blot assay. miR-27a-3p up-regulation by transfection with miR-27a-3p mimics attenuated SMMC-7721 and HepG2 cell viability, invasion as well as migration, obviously. Moreover, we found that dual specificity phosphatase 16 (DUSP16), also known as mitogen-activated protein kinase phosphatase 7 (MKP-7), is a target of miR-27a-3p. DUSP16 expression was obvious decrease by miR-27a-3p at both transcriptional and protein levels in both SMMC-7721 and HepG2 cells. DUSP16 expression in tissues of HCC was up-regulated in comparison with that in tissues of adjacent liver based on the TCGA database. Overexpression of DUSP16 significantly reversed the cell changes in viability, invasion and migration which resulted from miR-27a-3p up-regulation in SMMC-7721 and HepG2 cells. Our findings contribute to current understanding of the functions of miR-27a-3p and suggest a mechanism by which miR-27a-3p plays an anti-tumor role in the development of HCC by targeting DUSP16.