Upregulation of MIAT Regulates LOXL2 Expression by Competitively Binding MiR-29c in Clear Cell Renal Cell Carcinoma
Upregulation of MIAT Regulates LOXL2 Expression by Competitively Binding MiR-29c in Clear Cell Renal Cell Carcinoma
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DOI：
10.1159/000491974
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Yang, Hongmei
中科院分区：
文献类型：
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作者：
Qu, Yan;Xiao, Haibing;Yang, Hongmei
MIAT是一种长链非编码RNA（longnoncodingRNA，lncRNA），参与细胞增殖和肿瘤的发生发展。然而，MIAT在肾透明细胞癌（ccRCC）进展中的确切作用和分子机制仍不清楚。研究方法：我们在The Cancer Genome Atlas数据库中筛选了ccRCC的lncRNA谱，然后通过q-RT-PCR检测了45对ccRCC组织标本和细胞系中lncRNA MIAT的表达水平。进行MTS、集落形成、EdU和Transwell测定以检查MIAT对ccRCC增殖和转移的影响。进行蛋白质印迹和荧光素酶测定以确定MIAT是否可以通过竞争性结合ccRCC中的miR-29 c来调节Lox 12表达。结果：MIAT在ccRCC组织和细胞系中表达上调。MIAT高表达与临床病理特征差、生存率低相关。功能分析表明，敲低MIAT抑制肾癌细胞的增殖和转移在体外和体内。荧光素酶和蛋白质印迹分析进一步证实了miR-29 c与MIAT结合。此外，在患者样本中进一步验证了miR-29 c与MIAT和Lox 12的相关性。结论：提示MIAT可能是一种促进ccRCC增殖和转移的致癌性lncRNA，可能成为治疗ccRCC的潜在靶点。(C)2018作者（S）由S发布。Karger AG，巴塞尔
Background/Aims: MIAT is a long noncoding RNA (lncRNA) involved in cell proliferation and the development of tumor. However, the exact effects and molecular mechanisms of MIAT in clear cell renal cell carcinoma (ccRCC) progression are still unknown. Methods: We screened the lncRNAs' profile of ccRCC in The Cancer Genome Atlas database, and then examined the expression levels of lncRNA MIAT in 45 paired ccRCC tissue specimens and in cell lines by q-RT-PCR. MTS, colony formation, EdU, and Transwell assays were performed to examine the effect of MIAT on proliferation and metastasis of ccRCC. Western blot and luciferase assays were performed to determine whether MIAT can regulate Lox12 expression by competitively binding miR-29c in ccRCC. Results: MIAT was up-regulated in ccRCC tissues and cell lines. High MIAT expression correlated with worse clinicopathological features and shorter survival rate. Functional assays showed that knockdown of MIAT inhibited renal cancer cell proliferation and metastasis in vitro and in vivo. Luciferase and western blot assays further confirmed that miR-29c binds with MIAT. Additionally, the correlation of miR-29c with MIAT and Lox12 was further verified in patients' samples. Conclusion: Our data indicated that MIAT might be an oncogenic lncRNA that promoted proliferation and metastasis of ccRCC, and could be a potential therapeutic target in human ccRCC. (C) 2018 The Author(s) Published by S. Karger AG, Basel