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首页> 外文期刊>Cellular Physiology and Biochemistry >The Effects of miR-195-5p/MMP14 on Proliferation and Invasion of Cervical Carcinoma Cells Through TNF Signaling Pathway Based on Bioinformatics Analysis of Microarray Profiling
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The Effects of miR-195-5p/MMP14 on Proliferation and Invasion of Cervical Carcinoma Cells Through TNF Signaling Pathway Based on Bioinformatics Analysis of Microarray Profiling

机译：基于微阵列分析的生物信息学分析，miR-195-5p / MMP14通过TNF信号通路对宫颈癌细胞增殖和侵袭的影响

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Background/Aims This study is aimed at identification of miR-195-5p/MMP14 expression in cervical cancer (CC) and their roles on cell proliferation and invasion profile of CC cells through TNF signaling pathway in CC. Methods Microarray analysis, gene set enrichment analysis (GSEA) and DAVID were used to analyze differentially expressed miRNAs, mRNAs and signaling pathways. MiR-195-5p and MMP14 expression levels in CC cell were determined by qRT-PCR. Western blot was employed to measure MMP14 and TNF signaling pathway-relating protein level. Luciferase reporter system was used to confirm the targeting relationship between MMP14 and miR-195-5p. Cell proliferation and invasion was respectively deeded by CCK8, transwell. In vivo experiment was carried out to study the impact of MMP14 and miR-195-5p on CC development in mice. Results The microarray analysis and the results of qRT-PCR determined that miR-195-5p was under-expressed and MMP14 was over-expressed in CC cells. GSEA and DAVID analysis showed that TNF signaling pathway was regulated by miR-195-5p/MMP14 and activated in cervical carcinoma cells. The miR-195-5p and MMP14 have a negative regulation relation. In vivo experiment found that down-regulated MMP14 and up-regulated miR-195-5p suppressed the tumor development. Conclusion Our results suggest that MMP14 is a direct target of miR-195-5p, and down-regulated MMP14 and up-regulated miR-195-5p suppressed proliferation and invasion of CC cells by inhibiting TNF signaling pathway.
机译：背景/目的本研究旨在鉴定miR-195-5p / MMP14在宫颈癌（CC）中的表达以及它们通过CC中的TNF信号通路对CC细胞的增殖和侵袭特性的作用。方法采用微阵列分析，基因组富集分析（GSEA）和DAVID分析差异表达的miRNA，mRNA和信号通路。通过qRT-PCR确定CC细胞中的MiR-195-5p和MMP14表达水平。采用蛋白质印迹法检测MMP14和TNF信号通路相关蛋白水平。使用萤光素酶报告系统确认MMP14与miR-195-5p之间的靶向关系。细胞增殖和侵袭分别通过CCK8，transwell进行。进行了体内实验以研究MMP14和miR-195-5p对小鼠CC发育的影响。结果芯片分析和qRT-PCR结果表明，miR-195-5p在CC细胞中表达不足，而MMP14在CC细胞中过度表达。 GSEA和DAVID分析表明，TNF信号通路受miR-195-5p / MMP14调节并在宫颈癌细胞中被激活。 miR-195-5p和MMP14具有负调控关系。体内实验发现MMP14的下调和miR-195-5p的上调抑制了肿瘤的发展。结论我们的结果表明MMP14是miR-195-5p的直接靶标，而下调MMP14和上调miR-195-5p可通过抑制TNF信号通路抑制CC细胞的增殖和侵袭。

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