MiR-132 plays an oncogenic role in laryngeal squamous cell carcinoma by targeting FOXO1 and activating the PI3K/AKT pathway
MiR-132 plays an oncogenic role in laryngeal squamous cell carcinoma by targeting FOXO1 and activating the PI3K/AKT pathway
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DOI：
10.1016/j.ejphar.2016.10.015
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发表时间：
2016-12-05
影响因子：
5
通讯作者：
Yu, Wenfa
中科院分区：
文献类型：
--
作者：
Lian, Rong;Lu, Baocai;Yu, Wenfa
越来越多的证据表明，microrna的失调参与了肿瘤的进展和发展。本研究旨在探讨microRNA-132 （miR-132）在喉鳞状细胞癌（LSCC）中的表达及其功能。结果显示，miR-132在LSCC组织和细胞系中的表达明显上调。功能分析表明，miR132的过表达增强了细胞增殖和肿瘤生长，导致p27和p21下调，cyclin D1上调。此外，荧光素酶活性表明miR-132直接靶向FOXO1，并抑制LSCC细胞中FOXO1蛋白的表达。进一步研究发现，FOXO1的异位表达可以有效逆转miR-132诱导的细胞生长。此外，miR-132还激活了PI3K/AKT通路，进一步降低了FOXO1的表达。总之，这些发现表明miR-132在LSCC中通过在多个水平上调节PI3K/AKT/FOXO1通路发挥重要的致癌作用，从而具有很强的预后意义。因此，miR-132可能是LSCC的一种潜在治疗策略。
Increasing evidence indicates that the dysregulation of microRNAs is involved in tumor progression and development. The purpose of the present study was to explore the expression of microRNA-132 (miR-132) and its function in laryngeal squamous cell carcinoma (LSCC). The results showed that miR-132 expression was markedly upregulated in LSCC tissues and cell lines. Functional analyses indicated that overexpression of miR132 enhanced cell proliferation and tumor growth, which resulted in the downregulation of p27 and p21 and the upregulation of cyclin D1. In addition, luciferase activity indicated that miR-132 directly targets FOXO1, and inhibits FOXO1 protein expression in LSCC cells. Further studies revealed that the ectopic expression of FOXO1 effectively reversed the cell growth induced by miR-132. Moreover, miR-132 also activated the PI3K/AKT pathway, which further decreased FOXO1 expression. In conclusion, these findings demonstrated that miR-132 plays an important oncogenic role in LSCC by modulating the PI3K/AKT/FOXO1 pathway at multiple levels, resulting in strong prognostic implication. Therefore, miR-132 might be a potential therapeutic strategy in LSCC.