miR-144/451 cluster plays an oncogenic role in esophageal cancer by inhibiting cell invasion.
miR-144/451 cluster plays an oncogenic role in esophageal cancer by inhibiting cell invasion.
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miR-144/451簇通过抑制细胞侵袭在食管癌中发挥致癌作用
DOI：
10.1186/s12935-018-0679-8
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发表时间：
2018
影响因子：
5.8
通讯作者：
Liu R
中科院分区：
文献类型：
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作者：
Gao Z;Zhang P;Xie M;Gao H;Yin L;Liu R
miRNA簇在物种间广泛表达，越来越多的证据表明miRNA簇在肿瘤发生过程中比单个miRNA更有效。作为诊断和治疗的生物标志物，miRNA簇可能比单个miRNA更稳定和可靠。我们之前发现miR-144/451的低表达与食管癌的风险密切相关。对miR-144/451簇的研究多集中在单个miRNA而非整个miRNA簇，miRNA簇的调控机制在很大程度上是未知的。方法在本研究中，我们首先分析了microrna模拟物转染ECa9706后miR-144/451单个microrna的生物学功能。我们进一步分析了整个簇在稳定过表达miR-144/451的转基因细胞中的生物学功能。然后，我们在稳定的转基因细胞中进行全基因组mRNA微阵列检测差异表达基因谱。结果miR-144-3p过表达促进ECa9706细胞早期凋亡，抑制细胞迁移、细胞侵袭和细胞增殖。miR-144-5p和miR-451a抑制细胞增殖，同时miR-451a抑制细胞迁移。过表达miR-144/451导致细胞周期从S到G2和G2到M的阻滞，侵袭能力明显受到抑制。我们进一步观察到，在过表达miR-144/451的细胞中，c-Myc、p-ERK下调，而p53上调。在miR-144/451稳定的转基因细胞中，c-Myc、MMP9和p-cdc2的下游效应物下调。miR-144/451可能或部分地通过抑制ERK/c-Myc信号通路抑制ECa9706的细胞周期和侵袭。总的来说，我们从个体到整体水平分析了miR-144/451簇的功能。miR-144/451簇通过抑制细胞侵袭在食管癌中发挥原癌基因作用。
BackgroundmiRNA clusters are widely expressed across species, accumulating evidence has illustrated that miRNA cluster functioned more efficiently than single miRNA in cancer oncogenesis. It is likely that miRNA clusters are more stable and reliable than individual miRNA to be biomarkers for diagnosis and therapy. We previously found low expression of miR-144/451 was closely related with the risk for esophageal cancer. Researches on miR-144/451 cluster were mostly focused on individual miRNA but not the whole cluster, the regulatory mechanism of miRNA cluster were largely unknown.MethodsIn present study, we firstly analysed biological functions of individual miRNAs of miR-144/451 in ECa9706 transfected with miRNA mimics. We further analysed the biological function of the whole cluster in stable transgenic cell overexpressing miR-144/451. We then performed genome-wide mRNA microarray to detect differentially expressed gene profiles in stable transgenic cells.ResultsOverexpression of miR-144-3p promoted early apoptosis of ECa9706 and inhibited cell migration, cell invasion and cell proliferation. miR-144-5p and miR-451a inhibited cell proliferation, at the same time, miR-451a inhibited cell migration. Overexpression of miR-144/451 leads to the arrest cell cycle from S to G2 and G2 to M,while the invasion ability was obviously inhibited. We further observed c-Myc, p-ERK were downregulated in cells overexpressing miR-144/451, while p53 was up-regulated. The downstream effectors of c-Myc, MMP9 and p-cdc2 were downregulated in miR-144/451 stable transgenic cell. miR-144/451 may or partly inhibited cell cycles and invasion of ECa9706 through inhibiting ERK/c-Myc signaling pathway.ConclusionCollectively, we analysed the function of miR-144/451 cluster from individual to overall level. miR-144/451 cluster played proto oncogene role in esophageal cancer by inhibiting cell invasion.
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影响因子：
--
作者：
Liu Z;Miao T;Feng T;Jiang Z;Li M;Zhou L;Li H
通讯作者：
Li H
影响因子：
8.8
作者：
Matsushita R;Seki N;Chiyomaru T;Inoguchi S;Ishihara T;Goto Y;Nishikawa R;Mataki H;Tatarano S;Itesako T;Nakagawa M;Enokida H
通讯作者：
Enokida H
影响因子：
64.5
作者：
Pelengaris, S;Khan, M;Evan, GI
通讯作者：
Evan, GI
影响因子：
3.7
作者：
Babapoor S;Fleming E;Wu R;Dadras SS
通讯作者：
Dadras SS
DOI：
10.3109/10799893.2012.695798
发表时间：
2012-08
期刊：
Journal of receptor and signal transduction research
影响因子：
--
作者：
Chetram MA;Hinton CV
通讯作者：
Hinton CV