Long Non-Coding RNA LINC01572 Promotes Hepatocellular Carcinoma Progression via Sponging miR-195-5p to Enhance PFKFB4-Mediated Glycolysis and PI3K/AKT Activation.
Long Non-Coding RNA LINC01572 Promotes Hepatocellular Carcinoma Progression via Sponging miR-195-5p to Enhance PFKFB4-Mediated Glycolysis and PI3K/AKT Activation.
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长非编码 RNA LINC01572 通过海绵 miR-195-5p 增强 PFKFB4 介导的糖酵解和 PI3K/AKT 激活促进肝细胞癌进展
DOI：
10.3389/fcell.2021.783088
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发表时间：
2021
影响因子：
5.5
通讯作者：
Tang B
中科院分区：
文献类型：
--
作者：
Lai S;Quan Z;Hao Y;Liu J;Wang Z;Dai L;Dai H;He S;Tang B
背景：越来越多的证据表明，2型糖尿病(T2 DM)是肝细胞癌的危险因素，T2 DM相关的肝细胞癌是肝细胞癌的常见类型。在此，我们通过高通量筛查确定了一个在T2 DM相关肝癌中异常上调的LINC01572基因。在此基础上，本研究旨在探讨LINC01572在肝细胞癌发生发展中的作用和机制。方法：采用RT-qPCR方法检测LINC01572在肝细胞癌组织和细胞系中的表达。采用功能获得或功能丧失实验评价LINC01572在肝癌细胞增殖、迁移和侵袭中的体内外功能意义。通过生物信息学、RIP、RNA下拉和荧光素酶报告分析，探讨LINC01572/miR-195-5p/PFKFB4信号轴的调控关系。结果：在本研究中，我们用RNA测序的方法对T2 DM患者肝细胞癌组织及相应癌旁组织中的LncRNAs进行了分析。我们的数据显示，与对照组相比，LINC01572在肝癌组织中异常上调，特别是在合并T2 DM的肝癌组织中。LINC01572的高水平与晚期肿瘤分期、血HbA1c水平升高、生存期缩短相关。LINC01572的过表达显著促进了肝癌细胞的增殖、迁移、侵袭和上皮向间充质转化(EMT)，而LINC01572的过表达对肝癌细胞的作用则相反。一项机制研究表明，LINC01572通过海绵miR-195-5P上调PFKFB4水平，进而增强糖酵解和激活PI3K-AKT信号，从而调控肝癌的进展。结论：LINC01572作为miR-195-5p的CENA，抑制其对PFKFB4的抑制作用，从而促进糖酵解，激活PI3K/AKT信号通路，触发肝癌恶性转化。
Background: Accumulating evidence indicates that type 2 diabetes mellitus (T2DM) is a risk factor for hepatocellular carcinoma (HCC), and T2DM-associated HCC represents a common type of HCC cases. We herein identify an lncRNA LINC01572 that was aberrantly upregulated in T2DM-related HCC via high-throughput screening. Based on this, the study was undertaken to identify the functional role and mechanism of LINC01572 in HCC progression. Methods: RT-qPCR was used to detect the expressions of LINC01572 in HCC tissues and cell lines. Gain- or loss-of-function assays were applied to evaluate the in vitro and in vivo functional significance of LINC01572 in the HCC cell proliferation, migration, and invasion using corresponding experiments. Bioinformatics, RIP, RNA pull-down, and luciferase reporter assays were performed to explore the regulatory relationship of the LINC01572/miR-195-5p/PFKFB4 signaling axis. Result: In this study, we profiled lncRNAs in HCC tissues and corresponding adjacent tissues from HCC patients with T2DM by RNA sequencing. Our data showed that LINC01572 was aberrantly upregulated in HCC tissues as compared with control, especially in those with concurrent T2DM. The high level of LINC01572 was correlated with advanced tumor stage, increased blood HbA1c level, and shortened survival time. The overexpression of LINC01572 significantly promoted HCC cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition (EMT), while the knockdown of LINC01572 had the opposite effects on HCC cells. A mechanistic study revealed that LINC01572-regulated HCC progression via sponging miR-195-5p to increase the level of PFKFB4 and subsequent enhancement of glycolysis and activation of PI3K-AKT signaling. Conclusion: LINC01572 acts as ceRNA of miR-195-5p to restrict its inhibition of PFKFB4, thereby enhancing glycolysis and activates PI3K/AKT signaling to trigger HCC malignancy.
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