文章：

microRNA-9-5p通过抑制PDK4调控肝癌细胞线粒体功能

microRNA-9-5p regulates the mitochondrial function of hepatocellular carcinoma cells through suppressing PDK4 

原文发布日期：2020-11-30 

英文摘要：

Due to the lack of early diagnostic and effective treatment modalities, hepatocellular carcinoma (HCC) is still the most lethal cancer with a high mortality on a global scale. Recent studies have highlighted the key roles of microRNAs (miRs) in HCC development. In the study, we attempted to investigate the potential role of miR-9-5p in the progression of HCC. Expression of pyruvate dehydrogenase kinase 4 (PDK4) and miR-9-5p was examined in HCC tissues collected from HCC patients and cell lines. The proliferation, migration, invasion, and apoptosis of HCC cells, and levels of oxygen consumption rate, extracellular acidification rate and reactive oxygen species (ROS) as well as the tumorigenicity of transfected cells in vivo were measured after gain- and loss-of-function experiments in HCC cells. It was revealed that miR-9-5p was upregulated, while PDK4 was poorly expressed in HCC tissues and cells, associating with a poor prognosis of HCC patients. miR-9-5p directly targeted PDK4 and could downregulate its expression, thus leading to promoted cell proliferation, invasion and migration, enhanced mitochondrial activity and energy metabolism, and suppressed apoptosis in HCC cells, along with increased tumorigenicity in mouse xenograft models. Altogether, miR-9-5p facilitated mitochondrial energy metabolism of HCC cells by downregulating PDK4, promoting the development of HCC. miR-9-5p and PDK4 may serve as potential therapeutic targets for preventing recurrence and metastasis of HCC. 

摘要翻译： 

由于缺乏早期诊断和有效治疗手段，肝细胞癌（HCC）仍是全球范围内死亡率最高的致命癌症。近期研究揭示了微小RNA（miR）在HCC发展中的关键作用。本研究旨在探讨miR-9-5p在HCC进展中的潜在作用。我们检测了HCC患者癌组织及细胞系中丙酮酸脱氢酶激酶4（PDK4）和miR-9-5p的表达水平，并通过功能增益与缺失实验评估了HCC细胞的增殖、迁移、侵袭、凋亡能力、耗氧率、细胞外酸化率和活性氧（ROS）水平，以及转染细胞在体内的致瘤性。结果显示：miR-9-5p在HCC组织和细胞中表达上调，而PDK4呈低表达状态，且与HCC患者不良预后相关；miR-9-5p可直接靶向PDK4并下调其表达，从而促进HCC细胞增殖、侵袭和迁移，增强线粒体活性和能量代谢，抑制细胞凋亡，同时提高小鼠异种移植模型的致瘤性。综上，miR-9-5p通过下调PDK4促进HCC细胞线粒体能量代谢，进而推动HCC发展。miR-9-5p与PDK4可能成为预防HCC复发和转移的潜在治疗靶点。

原文链接：

microRNA-9-5p regulates the mitochondrial function of hepatocellular carcinoma cells through suppressing PDK4