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微小 RNA-198-5p 通过靶向岩藻糖基转移酶 8 抑制非小细胞肺癌细胞的迁移和侵袭。

MicroRNA-198-5p inhibits the migration and invasion of non-small lung cancer cells by targeting fucosyltransferase 8.

机构信息

Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China.

出版信息

Clin Exp Pharmacol Physiol. 2019 Oct;46(10):955-967. doi: 10.1111/1440-1681.13154. Epub 2019 Aug 30.

Abstract

MicroRNA-198-5p (miR-198-5p) displays crucial roles in various cancers including non-small cell lung cancer (NSCLC), but the underlying molecular mechanisms remain unclear. Fucosyltransferase 8 (FUT8) is associated with tumour metastasis and prognosis. In this study, we explored the expression of miR-198-5p and FUT8 in NSCLC patients. Results showed that miR-198-5p was under-expressed in NSCLC tissues and was negatively correlated with tumour size, lymph node metastasis and tumour-node-metastasis stage, while FUT8 expression was highly upregulated. Next, we altered miR-198-5p expression using the mimic or inhibitor in the functional study. Results showed that miR-198-5p overexpression could inhibit the migration, invasion and epithelial-to-mesenchymal transition (EMT) of NSCLC cells; reversely, suppression of miR-198-5p enhanced cell migration, invasion and EMT. In vivo, miR-198-5p overexpression inhibited the formation of mouse lung and liver metastasis. Luciferase reporter, real-time PCR and western blot assays showed that miR-198-5p could directly target FUT8 and regulate FUT8 expression. Further, FUT8 overexpression reversed the effect of miR-198-5p overexpression on the migration, invasion and EMT of NSCLC cells. Taken together, miR-198-5p functions as a tumour suppressor by targeting FUT8 in NSCLC. MiR-198-5p may be developed as a new diagnostic biomarker and therapeutic target for lung cancer.

摘要

miR-198-5p(miR-198-5p)在包括非小细胞肺癌(NSCLC)在内的各种癌症中发挥着重要作用,但潜在的分子机制尚不清楚。岩藻糖基转移酶 8(FUT8)与肿瘤转移和预后有关。在这项研究中,我们探讨了 miR-198-5p 和 FUT8 在 NSCLC 患者中的表达。结果表明,miR-198-5p 在 NSCLC 组织中表达下调,与肿瘤大小、淋巴结转移和肿瘤-淋巴结-转移分期呈负相关,而 FUT8 表达上调。接下来,我们在功能研究中使用模拟物或抑制剂改变 miR-198-5p 的表达。结果表明,miR-198-5p 过表达可抑制 NSCLC 细胞的迁移、侵袭和上皮间质转化(EMT);相反,抑制 miR-198-5p 增强了细胞迁移、侵袭和 EMT。在体内,miR-198-5p 过表达抑制了小鼠肺和肝转移的形成。荧光素酶报告、实时 PCR 和 Western blot 分析表明,miR-198-5p 可以直接靶向 FUT8 并调节 FUT8 的表达。进一步的,FUT8 过表达逆转了 miR-198-5p 过表达对 NSCLC 细胞迁移、侵袭和 EMT 的影响。综上所述,miR-198-5p 通过靶向 NSCLC 中的 FUT8 发挥肿瘤抑制作用。miR-198-5p 可能作为一种新的诊断生物标志物和治疗靶点用于肺癌。

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