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.

由于缺乏早期诊断和有效的治疗方式，肝细胞癌（HCC）仍然是全球范围内死亡率最高的癌症。最近的研究强调了 microRNA (miR) 在 HCC 发展中的关键作用。在这项研究中，我们试图研究 miR-9-5p 在 HCC 进展中的潜在作用。在从 HCC 患者和细胞系收集的 HCC 组织中检测丙酮酸脱氢酶激酶 4 (PDK4) 和 miR-9-5p 的表达。分别测定HCC细胞的增殖、迁移、侵袭和凋亡，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。 HCC细胞的功能实验。结果表明 miR-9-5p 被上调，而 PDK4 在 HCC 组织和细胞中表达较差，与 HCC 患者预后不良有关。miR-9-5p 直接靶向 PDK4 并可以下调其表达，从而促进细胞增殖、侵袭和迁移，增强线粒体活性和能量代谢，抑制 HCC 细胞凋亡，并增加小鼠异种移植模型的致瘤性。总之，miR-9-5p 通过下调 PDK4 促进 HCC 细胞的线粒体能量代谢，促进 HCC 的发展。miR-9-5p 和 PDK4 可作为预防 HCC 复发和转移的潜在治疗靶点。从而促进细胞增殖、侵袭和迁移，增强线粒体活性和能量代谢，抑制 HCC 细胞的凋亡，同时在小鼠异种移植模型中增加致瘤性。总之，miR-9-5p 通过下调 PDK4 促进 HCC 细胞的线粒体能量代谢，促进 HCC 的发展。miR-9-5p 和 PDK4 可作为预防 HCC 复发和转移的潜在治疗靶点。从而促进细胞增殖、侵袭和迁移，增强线粒体活性和能量代谢，抑制 HCC 细胞的凋亡，同时在小鼠异种移植模型中增加致瘤性。总之，miR-9-5p 通过下调 PDK4 促进 HCC 细胞的线粒体能量代谢，促进 HCC 的发展。miR-9-5p 和 PDK4 可作为预防 HCC 复发和转移的潜在治疗靶点。