Long non-coding RNA PVT1-5 promotes cell proliferation by regulating miR-126/SLC7A5 axis in lung cancer
Long non-coding RNA PVT1-5 promotes cell proliferation by regulating miR-126/SLC7A5 axis in lung cancer
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长非编码RNA PVT1-5通过调节肺癌中的miR-126/SLC7A5轴促进细胞增殖
DOI：
10.1016/j.bbrc.2017.12.114
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发表时间：
2018-01-15
影响因子：
3.1
通讯作者：
Zheng, Shangyong
中科院分区：
文献类型：
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作者：
Li, Hongliang;Chen, Shuxian;Zheng, Shangyong
调控异常的长非编码RNAs(LncRNAs)和微RNAs(MiRNAs)在人类癌症的发生发展中起着关键作用。据报道，IncRNA浆细胞瘤变异易位1(PVT1)是一种癌基因，与多种癌症有关。然而，PVT1-5及其相关miRNAs在肺癌中的作用还知之甚少。在本研究中，我们发现PVT1-5在肺癌组织和细胞系中的表达显著增加。通过用生物素标记的IncRNA-PVT1-5探针在肺癌细胞中进行miRNA体内沉淀(MiRIP)和双荧光素酶报告分析，我们确定miR-126与IncRNA-PVT1-5相关。此外，在细胞中敲除IncRNA-PVT1-5可以下调致癌miR-126的靶标SLC7A5的表达，从而导致细胞增殖。相反，抑制miR-126的表达显著增加SLC7A5的表达，减轻对细胞增殖的抑制。因此，我们的结果表明，IncRNA-PVT1-5可能通过调节miR126/SLC7A5通路而与miR-126竞争内源性RNA(CerNA)来促进细胞增殖，提示IncRNA-PVT1-5在肺癌的进展中起着关键作用，IncRNA-PVT1-5/miR-126/SLC7A5调控网络可能有助于肺癌的发生发展。(C)爱思唯尔公司出版的2017年。
Dysregulated long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play key roles in the development of human cancers. The IncRNA plasmacytoma variant translocation 1 (PVT1) is reported to be an oncogene in a variety of cancers. However, the roles of PVT1-5 and its related miRNAs in lung cancer are poorly understood. In this study, we found that PVT1-5 expression was significantly increased in lung cancer tissues and cell lines. By using biotin-labeled IncRNA-PVT1-5 probe for miRNA in vivo precipitation (miRIP) in lung cancer cells and dual-luciferase reporterassays, we identified that miR-126 was associated with IncRNA-PVT1-5. Furthermore, knockdown of IncRNA-PVT1-5 in cells could down regulate the expression of SLC7A5, the target of oncogenic miR-126, resulting in the cell proliferation. Conversely, inhibiting the expression of miR-126 markedly increased the expression of SLC7A5 and alleviated cell proliferation inhibition. Thus, our results indicated that IncRNA-PVT1-5 may function as a competing endogenous RNA (ceRNA) for miR-126 to promote cell proliferation by regulating the miR126/SLC7A5 pathway, suggesting that IncRNA-PVT1-5 plays a crucial role in lung cancer progression and IncRNA-PVT1-5/miR-126/SLC7A5 regulatory network may shed light on tumorigenesis in lung cancer. (C) 2017 Published by Elsevier Inc.