Long non-coding RNA FOXO1 inhibits lung cancer cell growth through down-regulating PI3K/AKT signaling pathway
Long non-coding RNA FOXO1 inhibits lung cancer cell growth through down-regulating PI3K/AKT signaling pathway
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DOI：
10.22038/ijbms.2019.31000.7480
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发表时间：
2019-05-01
影响因子：
2.2
通讯作者：
Sun, Yong
中科院分区：
文献类型：
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作者：
Ding, Xiaoqian;Wang, Qiang;Sun, Yong
目的：肺癌是最常见的恶性肿瘤之一，严重威胁着人们的健康和生命。最近，在乳腺癌中发现并研究了一种新的长非编码RNA（lncRNA），称为lncFOXO 1。然而，lncFOXO 1对肺癌的作用仍然不明确。本研究旨在探讨lncFOXO 1在肺癌细胞增殖、转移和凋亡中的作用。材料与方法：采用qRT-PCR方法检测肺癌组织或细胞中lncFOXO 1的表达水平。然后将lncFOXO 1过表达和敲低表达载体转染A549细胞，观察lncFOXO 1对A549细胞增殖、侵袭、迁移和凋亡的影响。这些实验分别使用MTT、集落形成、transwell、流式细胞术和western印迹分析进行评估。进行体内实验以使用异种移植肿瘤模型测定来检查肿瘤重量。结果：IncFOXO 1在肺癌组织和细胞（A549、H460、HCC 827和H1299）中的表达水平明显降低。IncFOXO 1基因的敲除可显著促进A549细胞的存活、集落形成和侵袭。然而，lncFOXO 1过表达明显逆转了结果。lncFOXO 1过表达可通过调节Bax、caspase-3和Bcl-2的表达而诱导A549细胞凋亡。体内实验表明，lncFOXO 1过表达抑制肿瘤重量。结论：LncFOXO 1通过下调PI 3 K/AKT信号通路抑制肺癌细胞增殖、转移和诱导凋亡。
Objective(s): Lung cancer is one of the most common malignant tumors, which seriously threatens the health and life of the people. Recently, a novel long non-coding RNA (lncRNA) termed lncFOXO1 was found and investigated in breast cancer. However, the effect of lncFOXO1 on lung cancer is still ambiguous. The current study aimed to uncover the functions of lncFOXO1 in lung cancer cell proliferation, metastasis and apoptosis.Materials and Methods: LncFOXO1 expression levels in lung cancer tissues or cells were detected using qRT-PCR. Then, overexpression and knockdown vectors of lncFOXO1 were transfected into A549 cells to investigate the effect of lncFOXO1 on cell proliferation, invasion, migration and apoptosis. These experiments were assessed using MTT, colony formation, transwell, flow cytometry and western blot assays, respectively. In vivo experiment was performed to examine the tumor weight using Xenograft tumor model assay. The important pathway of PI3K/AKT was finally examined using western blot.Results: The decreased expression level of lncFOXO1 was observed in lung cancer tissues and cells (A549, H460, HCC827 and H1299). Knockdown of lncFOXO1 significantly promoted A549 cells viability, colony formation and invasion. However, lncFOXO1 overexpression obviously reversed the results. Moreover, lncFOXO1 overexpression induced A549 cells apoptosis by regulating Bax, cleavedcaspase-3 and Bcl-2. In vivo experiment revealed that lncFOXO1 overexpression inhibited tumor weight. Furthermore, lncFOXO1 knockdown promoted colony formation and mediated Myc and Cyclin D1 expressions by regulating PI3K/AKT signaling pathway.Conclusion: LncFOXO1 inhibited lung cancer cell proliferation, metastasis, and induced apoptosis through down-regulating PI3K/AKT pathway.