Zhang Le, Kang Jiangang, Xin Benge, Cao Wei
Department of Interventional Radiology, The Second Affiliated Hospital of Air Force Medical University, Xi'an, China.
J Gastrointest Oncol. 2023 Apr 29;14(2):563-571. doi: 10.21037/jgo-23-149. Epub 2023 Apr 13.
N-Myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor, highly expressed in normal tissues but downregulated in many cancers. However, it has been shown to be involved in regulating glycolytic enzymes in clear cell renal cell carcinoma and colorectal cancer, although the mechanism is still not clear, and the function of NDRG2 in liver tumor glycolysis is completely unknown.
Liver tumor tissues were obtained from resected tumors and confirmed by pathological review. Immunohistochemical staining was performed to assess the protein expression of NDRG2. NDRG2-overexpressed and knockdown HepG2/SMMC-7721 cell lines were infected by lentivirus and cultured, before measurement of glucose uptake, lactate production, lactase dehydrogenase activity, and oxygen consumption rate. NDRG2 and SIRT1 proteins were analyzed by western blot.
Both the mRNA and protein levels of NDRG2 as a tumor suppressor were downregulated in the liver tumors and the survival rate of patients negatively correlated with the expression of NDRG2. In the NDRG2-overexpressed and knockdown cell lines, NDRG2 showed inhibition of glycolysis in liver tumor cells. Our experimental data suggested the expression of SIRT1 negatively correlated with that of NDRG2.
Our study findings enrich the understanding of the role of NDRG2 in tumor growth and of the mechanism by which NDRG2 regulates glycolysis. SIRT1, a deacetylase that plays an important role in glycolysis regulation, may be negatively regulated by NDRG2 in liver tumors.
N-Myc下游调控基因2（NDRG2）是一种肿瘤抑制因子，在正常组织中高表达，但在许多癌症中表达下调。然而，已表明它参与调控肾透明细胞癌和结直肠癌中的糖酵解酶，尽管其机制仍不清楚，且NDRG2在肝肿瘤糖酵解中的功能完全未知。
从切除的肿瘤中获取肝肿瘤组织，并经病理检查确认。进行免疫组织化学染色以评估NDRG2的蛋白表达。用慢病毒感染过表达和敲低NDRG2的HepG2/SMMC-7721细胞系并培养，然后测量葡萄糖摄取、乳酸生成、乳酸脱氢酶活性和耗氧率。通过蛋白质印迹分析NDRG2和SIRT1蛋白。
作为肿瘤抑制因子的NDRG2的mRNA和蛋白水平在肝肿瘤中均下调，且患者的生存率与NDRG2的表达呈负相关。在过表达和敲低NDRG2的细胞系中，NDRG2显示出对肝肿瘤细胞糖酵解的抑制作用。我们的实验数据表明SIRT1的表达与NDRG2的表达呈负相关。
我们的研究结果丰富了对NDRG2在肿瘤生长中的作用以及NDRG2调控糖酵解机制的理解。SIRT1是一种在糖酵解调控中起重要作用的去乙酰化酶，在肝肿瘤中可能受NDRG2负调控。
