miR-517a promotes Warburg effect in HCC by directly targeting FBP1
miR-517a promotes Warburg effect in HCC by directly targeting FBP1
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DOI：
10.2147/ott.s172084
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发表时间：
2018-01-01
影响因子：
4
通讯作者：
Huang, Jianzhao
中科院分区：
文献类型：
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作者：
Zhang, Delin;Li, Zhu;Huang, Jianzhao
目的：肝细胞癌是世界范围内侵袭性最强的恶性肿瘤之一。本研究的目的是探讨miR-517a在肝癌中的表达及其生物学功能。材料和方法：采用qRT-PCR方法检测miR-517a在临床标本和细胞系中的表达。采用CKK-8实验和集落形成实验检测miR-517a对细胞增殖的调控作用。检测葡萄糖摄取和乳酸生成以确定Warburg效应。我们还使用SeaHorse系统进行了ECAR分析。用荧光素酶活性测定法检测miR-517a与FBP1 3‘UTR的结合。结果：miR-517a在肝癌组织中表达上调。此外，miR-517a过表达促进了细胞增殖和Warburg效应。从机制上讲，miR-517a可以直接靶向FBP1的3‘-非编码区。结论：miR-517a作为癌基因促进了肝细胞癌的Warburg效应，有利于肿瘤生长，miR-517a/FBP1可能成为治疗肝癌的新靶点。
Purpose: Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies world-wide. Our aim is to explore the expression and biological function of miR-517a in HCC.Materials and methods: We performed qRT-PCR to detect the expression of miR-517a in clinical samples and cell lines. CKK-8 assay and colony formation assay were employed to detect the miR-517a regulated cell proliferation. Glucose uptake and lactate production were examined to determine the Warburg effect. We also performed ECAR assay using Seahorse system. Luciferase acitivy assay was used to examine the binding of FBP1 3'UTR by miR-517a.Results: miR-517a was upregulated in HCC samples in both genomic and mRNA levels. More-over, overexpression of miR-517a promoted cell proliferation and Warburg effect. Mechanically, miR-517a could directly target the 3'-UTR of FBP1. In addition, restoring the expression of FBP1 inhibited cell growth.Conclusion: We demonstrated that miR-517a acts as an oncogene to promote Warburg effect in HCC, favoring tumor growth, and miR-517a/FBP1 could be a novel target for HCC treatment.