Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Bioengineered. 2022 Mar;13(3):5344-5356. doi: 10.1080/21655979.2021.2017630.
Optic atrophy 3 (OPA3) is an integral protein of the mitochondrial outer membrane. The current study explored the expression of in hepatocellular carcinoma (HCC), its association with the prognosis and its involvement in HCC cell proliferation and aerobic glycolysis. In addition, the transcription factors that activate its expression were screened and validated. Gene expression data in normal liver and liver cancer were acquired from the Genotype-Tissue Expression Project (GTEx) and The Cancer Genome Atlas (TCGA)-Liver Hepatocellular Carcinoma (TCGA-LIHC). Chromatin immunoprecipitation-seq data (GSM1010876) in Cistrome Data Browser was used for searching transcriptional factors binding to the promoter. HCC cell lines HLF and JHH2 were used for and studies. Results showed that is significantly upregulated in HCC and associated with unfavorable prognosis. knockdown impaired HCC cell growth and . Besides, it decreased glucose uptake, lactate production, intracellular ATP levels, and extracellular acidification rate (ECAR) of HLF and JHH2 cells. MYB Proto-Oncogene Like 2 (MYBL2) can bind to the promoter of and enhance its transcription. knockdown decreased aerobic glycolysis in HCC cells. overexpression reversed these alterations. In conclusion, this study revealed a novel MYBL2-OPA3 axis that enhances HCC cell proliferation and aerobic glycolysis.
视神经萎缩 3 型(OPA3)是线粒体外膜的一种整合蛋白。本研究探讨了其在肝细胞癌(HCC)中的表达及其与预后的关系,以及其在 HCC 细胞增殖和有氧糖酵解中的作用。此外,还筛选并验证了激活其表达的转录因子。从基因表达综合数据库(GTEx)和癌症基因组图谱(TCGA)-肝脏肝癌(TCGA-LIHC)中获取正常肝脏和肝癌的基因表达数据。使用 Cistrome 数据浏览器中的染色质免疫沉淀测序数据(GSM1010876)来搜索与 启动子结合的转录因子。HLF 和 JHH2 HCC 细胞系用于 和 研究。结果表明,OPA3 在 HCC 中显著上调,与不良预后相关。OPA3 敲低可损害 HCC 细胞生长和。此外,OPA3 敲低还降低了 HLF 和 JHH2 细胞的葡萄糖摄取、乳酸生成、细胞内 ATP 水平和细胞外酸化率(ECAR)。原癌基因 MYB 样 2(MYBL2)可与 OPA3 的启动子结合并增强其转录。OPA3 敲低可降低 HCC 细胞的有氧糖酵解。OPA3 过表达可逆转这些改变。总之,本研究揭示了一种新的 MYBL2-OPA3 轴,可增强 HCC 细胞的增殖和有氧糖酵解。