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miR-3691-5p promotes hepatocellular carcinoma cell migration and invasion through activating PI3K/Akt signaling by targeting PTEN

机译:miR-3691-5p通过靶向PTEN激活PI3K / Akt信号传导来促进肝癌细胞的迁移和侵袭

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Background: The enhanced ability of cancer metastasis is the major cause for the cancer-related death of hepatocellular carcinoma (HCC). Better understanding the mechanisms for the motility of cancer cells will benefit the treatment. Accumulating evidence suggests that aberrant microRNA (miRNA) expression contributes to HCC development and progression, whereas miR-3691-5p has not been reported in HCC. Purpose: The aim of this study was to elucidate the expression, function and mechanism of miR-3691-5p in HCC. Methods: Real-time quantitative polymerase chain reaction (qPCR) was performed to detect miR-3691-5p expression in HCC tissues and cell lines database analysis were conducted for detection of the expression of miR-3691-5p in HCC. Then, the association of miR-3691-5p with clinicopathological features of HCC patients were statistically measured. Subsequently, we attempted to observe the effects of miR-3691-5p on migration and invasion of HCC cells by transwell assays. Furthermore, bioinformatics tools and luciferase reporter gene assay as well as recuse experiments were conducted to explore the target of miR-3691-5p in HCC, and to explore whether the target mediated the effects of miR-3691-5p HCC cells. Results: In the current study, we found that miR-3691-5p expression was elevated in both HCC tissues and cell lines, which was significantly correlated with poor prognosis and clinicopathological features including TNM stage ( P =0.016) and vascular invasion ( P =0.016). Furthermore, gain-or loss-of function assays demonstrated that miR-3691-5p promoted HCC cell migration and invasion. Luciferase reporter assay confirmed that PTEN was a direct downstream target of miR-3691-5p. Recuse assays showed that restoration of PTEN reversed the effects of miR-3691-5p on HCC cell migration and invasion through decreasing PI3K/Akt signaling. Conclusion: Our results demonstrated that miR-3691-5p contributes to HCC cell migration and invasion through activating PI3K/Akt signaling by targeting PTEN.
机译:背景:增强的癌症转移能力是导致肝细胞癌(HCC)与癌症相关的死亡的主要原因。更好地了解癌细胞运动的机制将有益于治疗。越来越多的证据表明,异常的microRNA(miRNA)表达有助于HCC的发展和进程,而在HCC中尚未报道miR-3691-5p。目的:本研究的目的是阐明miR-3691-5p在肝癌中的表达,功能和机制。方法:采用实时定量聚合酶链反应(qPCR)检测miR-3691-5p在肝癌组织中的表达,并通过细胞系数据库分析检测miR-3691-5p在肝癌组织中的表达。然后,统计测量miR-3691-5p与HCC患者临床病理特征之间的关系。随后,我们尝试通过transwell分析观察miR-3691-5p对HCC细胞迁移和侵袭的影响。此外,进行了生物信息学工具和荧光素酶报告基因测定以及再利用实验,以探索miR-3691-5p在肝癌中的靶标,并探讨该靶标是否介导miR-3691-5p HCC细胞的作用。结果:在当前研究中,我们发现miR-3691-5p在肝癌组织和细胞系中均表达升高,这与不良预后和临床病理特征(包括TNM分期(P = 0.016)和血管浸润)相关(P = 0.016)。此外,功能获得或丧失的测定证明miR-3691-5p促进了HCC细胞的迁移和侵袭。萤光素酶报告基因测定证实PTEN是miR-3691-5p的直接下游靶标。回收测定表明,PTEN的恢复通过降低PI3K / Akt信号传导,逆转了miR-3691-5p对HCC细胞迁移和侵袭的作用。结论:我们的结果表明,miR-3691-5p通过靶向PTEN激活PI3K / Akt信号传导,有助于HCC细胞迁移和侵袭。

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