Yang Xuejing, Feng Huijing, Kim Jonghwa, Ti Gang, Wang Lin, Wang Kun, Song Dong
Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan 030032, China.
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Acta Biochim Biophys Sin (Shanghai). 2024 May 22;56(11):1604-1617. doi: 10.3724/abbs.2024083.
LncRNA PRR34-AS1 overexpression promotes the proliferation and invasion of hepatocellular carcinoma (HCC) cells, but whether it affects HCC energy metabolism remains unclear. Mitochondrial division and glycolytic reprogramming play important roles in tumor development. In this study, the differential expression of PRR34-AS1 is explored via TCGA analysis, and higher levels of PRR34-AS1 are detected in patients with liver cancer than in healthy individuals. A series of experiments, such as CCK-8, PCR, and immunofluorescence staining, reveal that the proliferation, invasion, glycolysis, and mitochondrial division of PRR34-AS1-overexpressing hepatoma cells are significantly promoted. TCGA analysis and immunohistochemistry reveal high expression of the mitochondrial dynamin MIEF2 in liver cancer tissues. Dual-luciferase reporter assays confirm that miR-498 targets and binds to mitochondrial elongation factor 2 (MIEF2). In addition, we show that PRR34-AS1 can sponge miR-498. Therefore, we further investigate the effects of the lncRNA PRR34-AS1/miR-498/MIEF2 axis on the growth, glucose metabolism, and mitochondrial division in hepatocellular carcinoma cells. A series of experiments are performed on hepatocellular carcinoma cells after different treatments. The results show that the proliferative activity, invasive ability, and glycolytic level of hepatocellular carcinoma cells are decreased in HCC cells with low PRR34-AS1 expression, and the miR-498 expression level is increased in these cells. Inhibition of miR-498 or overexpression of MIEF2 restored the proliferative activity, invasive ability, glycolysis, and mitochondrial division in hepatocellular carcinoma cells. Thus, PRR34-AS1 regulates MIEF2 by sponging miR-498, thereby promoting mitochondrial division, mediating glycolytic reprogramming and ultimately driving the growth and invasion of HCC cells. Furthermore, mouse experiments yield results similar to those of the experiments, verifying the above results.
长链非编码RNA PRR34-AS1的过表达促进肝细胞癌（HCC）细胞的增殖和侵袭，但其是否影响HCC的能量代谢仍不清楚。线粒体分裂和糖酵解重编程在肿瘤发展中起重要作用。在本研究中，通过TCGA分析探索PRR34-AS1的差异表达，发现肝癌患者中PRR34-AS1水平高于健康个体。一系列实验，如CCK-8、PCR和免疫荧光染色，显示PRR34-AS1过表达的肝癌细胞的增殖、侵袭、糖酵解和线粒体分裂均显著增强。TCGA分析和免疫组化显示肝癌组织中线粒体动力蛋白MIEF2高表达。双荧光素酶报告基因实验证实miR-498靶向并结合线粒体延伸因子2（MIEF2）。此外，我们发现PRR34-AS1可以吸附miR-498。因此，我们进一步研究lncRNA PRR34-AS1/miR-498/MIEF2轴对肝癌细胞生长、葡萄糖代谢和线粒体分裂的影响。对经过不同处理的肝癌细胞进行了一系列实验。结果显示，PRR34-AS1低表达的肝癌细胞中，其增殖活性、侵袭能力和糖酵解水平降低，而这些细胞中miR-498表达水平升高。抑制miR-498或过表达MIEF2可恢复肝癌细胞的增殖活性、侵袭能力、糖酵解和线粒体分裂。因此，PRR34-AS1通过吸附miR-498来调节MIEF2，从而促进线粒体分裂，介导糖酵解重编程，最终推动HCC细胞的生长和侵袭。此外，小鼠实验结果与上述实验相似，验证了上述结果。
