Long non-coding RNA KCNQ1OT1 mediates the growth of hepatocellular carcinoma by functioning as a competing endogenous RNA of miR-504
Long non-coding RNA KCNQ1OT1 mediates the growth of hepatocellular carcinoma by functioning as a competing endogenous RNA of miR-504
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长非编码 RNA KCNQ1OT1 通过作为 miR-504 的竞争性内源 RNA 介导肝细胞癌的生长。
DOI：
10.3892/ijo.2018.4313
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发表时间：
2018-05-01
影响因子：
5.2
通讯作者：
Liu, Chang
中科院分区：
文献类型：
--
作者：
Li, Chao;Miao, Runchen;Liu, Chang
越来越多的证据表明，长链非编码RNA（lncRNA）是肝细胞癌（HCC）生长的关键因素。lncRNA KCNQ 1反链/反义转录本1（KCNQ 1 OT 1）的失调已在许多人类良性疾病中报道。然而，KCNQ 1 OT 1在人类HCC中的作用仍然知之甚少。在这项研究中，我们证明了KCNQ 1 OT 1的表达在肝癌组织中异常增加。KCNQ 1 OT 1的异位高表达与肝硬化、肿瘤较大、TNM分期较晚、总生存率和无瘤生存率较低相关。据我们所知，我们第一次报道KCNQ 1 OT 1敲低导致细胞活力和集落形成能力降低，体外凋亡率增加。来自我们的体内结果的结果表明，KCNQ 1 OT 1沉默通过损害细胞增殖来减弱肿瘤生长。此外，我们发现KCNQ 1 OT 1发挥其作用部分依赖于microRNA-504（miR-504）介导的细胞周期蛋白依赖性激酶16（CDK 16）的调节，除了糖原合成酶激酶3（GSK 3）/-catenin/Bcl-2信号通路的调节。本研究揭示了lncRNA KCNQ 1 OT 1在促进肝癌生长中的功能和作用机制。因此，lncRNA KCNQ 1 OT 1可能被证明是人HCC的潜在治疗靶点。
Accumulating evidence highlights the fact that long non-coding RNAs (lncRNAs) serve as critical factors in the growth of hepatocellular carcinoma (HCC). The dysregulation of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) has been reported in numerous human benign diseases. However, the role of KCNQ1OT1 in human HCC remains poorly understood. In this study, we demonstrated that the expression of KCNQ1OT1 was abnormally increased in HCC tissues. The ectopic high expression of KCNQ1OT1 was associated with liver cirrhosis, a larger tumor size, an advanced TNM stage, and a worse overall survival and tumor-free survival. For the first time, to the best of our knowledge, we report that KCNQ1OT1 knockdown results in a decreased cell viability and colony formation ability, and an increased rate of apoptosis in vitro. The results from our in vivo results demonstrated that KCNQ1OT1 silencing attenuated tumor growth by impairing cell proliferation. Additionally, we found that KCNQ1OT1 exerted its effects partly by relying on the microRNA-504 (miR-504)-mediated regulation of cyclin-dependent kinase 16 (CDK16), in addition to the regulation of the glycogen synthase kinase 3 (GSK3)/-catenin/Bcl-2 signaling pathway. The present study revealed the functions and mechanisms of action of lncRNA KCNQ1OT1 regarding its role in promoting the growth of HCC. Thus, lncRNA KCNQ1OT1 may prove to be a potential therapeutic target for human HCC.