Minimally Invasive Therapy Center, Department of Integrative Oncology, Fudan University, Shanghai Cancer Center, 270 Dong'An Road, Shanghai, 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Biol Direct. 2024 Aug 26;19(1):74. doi: 10.1186/s13062-024-00513-x.
Excavation of key molecules can help identify therapeutic targets and improve the prognosis of pancreatic cancer. This study evaluated the roles of SUMO3 in cell viability, glycolysis, gemcitabine (GEM) sensitivity, and the antitumor activity of butyric acid (BA) in pancreatic cancer.
The mRNA and protein levels of SUMO3 were detected by qRT-PCR, Western blot, and immunohistochemical assay. SUMO3 was silenced or overexpressed in pancreatic cancer cells with or without Wnt/β-catenin pathway inhibitor, glycolysis inhibitor, GEM, or BA treatment. Cell viability was measured using the Cell Counting Kit-8 assay. Glycolysis was measured by determining the extracellular acidification rate, ATP level, and lactate content. Apoptosis was measured by flow cytometry, and TUNEL staining was used to examine in vitro and in vivo sensitivity to GEM chemotherapy. Luciferase reporter and chromatin immunoprecipitation assays were conducted to detect the binding of the SUMO3 promoter and NF-κB p65.
SUMO3 was increased and associated with poor survival in pancreatic cancer. SUMO3 knockdown decreased cell viability and glycolysis in vitro and inhibited tumor growth in vivo. SUMO3 overexpression increased cell viability and glycolysis in vitro through the β-catenin pathway. SUMO3 knockdown increased GEM sensitivity, whereas SUMO3 overexpression decreased GEM sensitivity and inhibited the antitumor activity of BA. BA promoted histone acetylation and p-IκBα expression to inhibit NF-κB p65-mediated SUMO3 transcription.
SUMO3 acted as an active molecule in cell survival and growth by enhancing glycolysis in response to either GEM or BA. The mechanism was related to the constitutive IκBα/NF-κB/SUMO3/β-catenin signaling pathway.
挖掘关键分子有助于确定治疗靶点，改善胰腺癌的预后。本研究评估了 SUMO3 在胰腺癌细胞活力、糖酵解、吉西他滨（GEM）敏感性以及丁酸（BA）的抗肿瘤活性中的作用。
通过 qRT-PCR、Western blot 和免疫组织化学检测 SUMO3 的 mRNA 和蛋白水平。用 Wnt/β-catenin 通路抑制剂、糖酵解抑制剂、GEM 或 BA 处理胰腺癌细胞，沉默或过表达 SUMO3。用细胞计数试剂盒-8 检测细胞活力。通过测定细胞外酸化率、ATP 水平和乳酸含量来检测糖酵解。用流式细胞术检测细胞凋亡，用 TUNEL 染色检测体内外对 GEM 化疗的敏感性。用荧光素酶报告基因和染色质免疫沉淀检测 SUMO3 启动子和 NF-κB p65 的结合。
SUMO3 在胰腺癌中表达增加且与不良预后相关。SUMO3 敲低降低了体外细胞活力和糖酵解，抑制了体内肿瘤生长。SUMO3 过表达通过 β-catenin 通路增加了体外细胞活力和糖酵解。SUMO3 敲低增加了 GEM 的敏感性，而过表达则降低了 GEM 的敏感性并抑制了 BA 的抗肿瘤活性。BA 通过促进组蛋白乙酰化和 p-IκBα 表达来抑制 NF-κB p65 介导的 SUMO3 转录。
SUMO3 通过增强糖酵解来应对 GEM 或 BA，作为细胞存活和生长的活性分子发挥作用。其机制与组成性 IκBα/NF-κB/SUMO3/β-catenin 信号通路有关。
