Regulation of proliferation, angiogenesis and apoptosis in hepatocellular carcinoma by miR-26b-5p
Regulation of proliferation, angiogenesis and apoptosis in hepatocellular carcinoma by miR-26b-5p
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miR-26b-5p对肝细胞癌增殖、血管生成和凋亡的调节
DOI：
10.1007/s13277-016-4964-7
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发表时间：
2016-08-01
期刊：
影响因子：
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通讯作者：
An, Jindan
中科院分区：
文献类型：
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作者：
Wang, Yong;Sun, Baocun;An, Jindan
微小RNA（microRNAs，miRNAs）在肝细胞癌（hepatocellular carcinoma，HCC）的细胞增殖、分化和凋亡中起着重要作用。miR-26 b已被证实是肿瘤发生和其他病理过程中的重要调节因子。miR-26 b-5 p是成熟miR-26家族的成员之一，其在HCC增殖、血管生成和凋亡中的作用尚不清楚。在此，我们通过实时定量聚合酶链反应（qRT-PCR）证实，与正常肝组织和肝细胞相比，HCC组织和HCC细胞系中miR-26 b-5 p的表达显著降低。进一步分析miR-26 b-5 p与HCC患者临床特征的关系，发现miR-26 b-5 p与HCC细胞分化程度呈正相关。进一步使用计算搜索来鉴定HCC细胞中miR-26 b-5 p的下游靶标和信号传导途径。通过刮取、3-（4，5-二甲基噻唑-2-基）-2，5-二苯基四唑溴化物（MTT）和三维培养测定来评估细胞活力、增殖和管形成能力，以证实miR-26 b-5 p抑制HCC细胞生长并损害HCC细胞的管形成能力。体内外研究表明，miR-26 b-5 p可通过下调VE-cadherin、Snail和MMP 2的表达，抑制肝癌细胞血管拟态（VM）和血管生成，并抑制肝癌细胞凋亡。使用小鼠模型，我们发现与来自对照细胞的肿瘤相比，来自表达miR-26 b-5 p的HCC细胞的肿瘤显示出微血管密度的显著降低。因此，我们的数据提供了进一步了解miR-26 b-5 p作为HCC中增殖、血管生成和凋亡的负调节因子的作用。
MicroRNAs (miRNAs) play vital roles in cell proliferation, differentiation and apoptosis in hepatocellular carcinoma (HCC). miR-26b has been confirmed as an important regulator in carcinogenesis and other pathological processes. miR-26b-5p is one member of the mature miR-26 family, and its functional role in proliferation, angiogenesis and apoptosis in HCC remains unknown. Here, we demonstrate that miR-26b-5p expression was significantly decreased in HCC tissues and HCC cell lines compared with normal liver tissues and liver cells by quantitative real-time polymerase chain reaction (qRT-PCR). The relationships between miR-26b-5p and the clinical characteristics of HCC patients were further analysed, and miR-26b-5p was positively correlated with the differentiation of HCC cells. Computational searches were further used to identify the downstream targets and signalling pathways of miR-26b-5p in HCC cells. Cell viability, proliferation and tube formation abilities were assessed by scrape, 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and three-dimensional culture assays to confirm that miR-26b-5p inhibited HCC cell growth and impaired the tube formation ability of the HCC cells. Both in vitro and in vivo studies showed that miR-26b-5p could suppress vascular mimicry (VM) and angiogenesis by down-regulating the expression of VE-cadherin, Snail and MMP2 and could inhibit the apoptosis of HCC cells. Using mouse models, we revealed that tumours derived from miR-26b-5p-expressing HCC cells displayed a significant decrease in microvessel density compared with those derived from control cells. Therefore, our data provide further insight into the role of miR-26b-5p as a negative regulator of proliferation, angiogenesis, and apoptosis in HCC.