CircFOXK2 promotes hepatocellular carcinoma progression and leads to a poor clinical prognosis via regulating the Warburg effect.
CircFOXK2 promotes hepatocellular carcinoma progression and leads to a poor clinical prognosis via regulating the Warburg effect.
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DOI：
10.1186/s13046-023-02624-1
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发表时间：
2023-03-15
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影响因子：
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Warburg 效应已被证实对肿瘤进展至关重要，也是肝细胞癌 (HCC) 患者临床结果不佳的原因。越来越多的文献表明，环状 RNA (circRNA) 是 HCC 的重要调节因子。然而，迄今为止，很少有涉及 HCC Warburg 效应的 circRNA 被研究过。在此，我们旨在探讨 circFOXK2 对 HCC 葡萄糖代谢重编程的贡献。本研究设计了不同的引物鉴定了14个源自FOXK2基因的circRNA，并筛选了它们在HCC和癌旁肝组织中的差异表达。最终，选择circFOXK2（hsa_circ_0000817）进行进一步研究。接下来，评估了circFOXK2的临床意义。然后，我们评估了 circFOXK2 的促癌活性及其对 HCC 细胞系和动物异种移植物中 Warburg 效应的影响。最后探讨了circFOXK2调控HCC Warburg效应的分子机制。 CircFOXK2 在 HCC 组织中异常上调，并且与接受根治性肝切除术的患者不良临床结果呈正相关。 circFOXK2 沉默可在体外和体内显着抑制 HCC 进展。从机制上讲，circFOXK2上调蛋白FOXK2-142aa的表达，促进LDHA磷酸化，并通过调节miR-484/Fis1途径导致线粒体裂变，最终激活HCC中的Warburg效应。 CircFOXK2 是 HCC 的预后生物标志物，它通过促进导致肿瘤进展的蛋白质和 miRNA 海绵的表达来促进 Warburg 效应。总体而言，circFOXK2 作为 HCC 患者的潜在治疗靶点具有巨大的前景。在线版本包含可在 10.1186/s13046-023-02624-1 获取的补充材料。
The Warburg effect is well-established to be essential for tumor progression and accounts for the poor clinical outcomes of hepatocellular carcinoma (HCC) patients. An increasing body of literature suggests that circular RNAs (circRNAs) are important regulators for HCC. However, few circRNAs involved in the Warburg effect of HCC have hitherto been investigated. Herein, we aimed to explore the contribution of circFOXK2 to glucose metabolism reprogramming in HCC. In the present study, different primers were designed to identify 14 circRNAs originating from the FOXK2 gene, and their differential expression between HCC and adjacent liver tissues was screened. Ultimately, circFOXK2 (hsa_circ_0000817) was selected for further research. Next, the clinical significance of circFOXK2 was evaluated. We then assessed the pro-oncogenic activity of circFOXK2 and its impact on the Warburg effect in both HCC cell lines and animal xenografts. Finally, the molecular mechanisms of how circFOXK2 regulates the Warburg effect of HCC were explored. CircFOXK2 was aberrantly upregulated in HCC tissues and positively correlated with poor clinical outcomes in patients that underwent radical hepatectomy. Silencing of circFOXK2 significantly suppressed HCC progression both in vitro and in vivo. Mechanistically, circFOXK2 upregulated the expression of protein FOXK2-142aa to promote LDHA phosphorylation and led to mitochondrial fission by regulating the miR-484/Fis1 pathway, ultimately activating the Warburg effect in HCC. CircFOXK2 is a prognostic biomarker of HCC that promotes the Warburg effect by promoting the expression of proteins and miRNA sponges that lead to tumor progression. Overall, circFOXK2 has huge prospects as a potential therapeutic target for patients with HCC. The online version contains supplementary material available at 10.1186/s13046-023-02624-1.
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DOI：
10.1158/1078-0432.ccr-13-0304
发表时间：
2013-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
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作者：
Linehan WM;Rouault TA
通讯作者：
Rouault TA
circFNDC3B编码的新型蛋白质通过调节结肠癌中的Snail抑制肿瘤进展和EMT
影响因子：
37.3
作者：
Pan, Zihao;Cai, Jianye;Zhang, Lei
通讯作者：
Zhang, Lei
SIK2 通过 PI3K/AKT/HIF-1 α 通路和 Drp1 介导的卵巢癌线粒体裂变促进葡萄糖代谢重编程
影响因子：
9.7
作者：
Gao, Tian;Zhang, Xiaohong;Liu, Shujuan
通讯作者：
Liu, Shujuan
circRNA生物合成的调控
影响因子：
4.1
作者：
Chen, Ling-Ling;Yang, Li
通讯作者：
Yang, Li
环状 RNA 测序确定 CircASAP1 是肝细胞癌转移的关键调节因子。
影响因子：
13.5
作者：
Hu, Zhi-Qiang;Zhou, Shao-Lai;Zhou, Jian
通讯作者：
Zhou, Jian