Long non-coding RNA FER1L4 inhibits cell proliferation and metastasis through regulation of the PI3K/AKT signaling pathway in lung cancer cells

Long non-coding RNA FER1L4 inhibits cell proliferation and metastasis through regulation of the PI3K/AKT signaling pathway in lung cancer cells
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DOI:
10.3892/mmr.2019.10219
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发表时间:
2019-07-01
影响因子:
3.4
通讯作者:
Yang, Yuping
Yang, Yuping
中科院分区:
医学4区
文献类型:
--
作者:
Gao, Xuejin;Wang, Nianchang;Yang, Yuping

文献摘要

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肺癌是世界上最常见的恶性肿瘤之一,然而,目前对其详细机制的了解仍然有限。长非编码RNA(LncRNAs)在肿瘤发生中起重要作用。本研究旨在探讨一个新的lncRNA,Fer-1样家族成员4(FER1L4)在肺肿瘤发生中的作用。本研究通过逆转录定量聚合酶链式反应分析证实,FER1L4在临床肺癌组织和培养的肺癌细胞中的表达水平显著降低。集落形成实验、细胞增殖实验和Transwell实验分别检测FER1L4在肺癌细胞系A549和95D中的过表达抑制集落形成、细胞增殖和细胞迁移能力。FER1L4过表达导致A549和95D细胞中磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)的表达水平降低,而用小分子磷酸酶抑制剂和张力蛋白同源物激活PI3K/Akt信号通路,逆转了FER1L4对细胞增殖和转移的抑制作用。以上结果提示,lncRNA FER1L4通过抑制PI3K/Akt信号通路抑制肺癌细胞的增殖和转移。
Lung cancer is among the most common malignancies worldwide; however, the current understanding of its detailed mechanism remains limited. Long non-coding RNAs (lncRNAs) were previously identified to serve significant roles in tumorigenesis. The present study aimed to investigate the role of a novel lncRNA, Fer-1-like family member 4 (FER1L4), in lung tumorigenesis. In the present study, it was demonstrated that the expression level of FER1L4 was significantly decreased in clinical lung cancer tissues and in cultured lung cancer cells, as evidenced by reverse transcription-quantitative polymerase chain reaction analysis. Overexpression of FER1L4 in lung cancer cell lines A549 and 95D inhibited colony formation, cell proliferation and cell migration capacity, measured by colony formation assays, cell proliferation assays and Transwell assays, respectively. Overexpression of FER1L4 led to a reduction in the expression levels of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) in A549 and 95D cells, whereas, activation of PI3K/Akt signaling using a small molecular inhibitor of phosphatase and tensin homolog, reversed the inhibitory effects of FER1L4 on cell proliferation and metastasis. All of these results suggested that the lncRNA FER1L4 suppressed cell proliferation and metastasis by inhibiting the PI3K/Akt signaling pathway in lung cancer.