SUMOylated hnRNPM抑制PFKFB3酸化以调节糖解和瘤发生
Ya-Xian Zhong1, Huan-Bin Zhao2, Meng-Han Lian3
1Institute of Aging & Tissue Regeneration, Stress and Cancer Research Unit of Chinese Academy of Medical Sciences (No. 2019RU043), State Key Laboratory of Systems Medicine for Cancer, Ren-Ji Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200127, China; Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, SJTU-SM, Shanghai, 200025, China.
异质核核核糖核蛋白M (hnRNPM) 的SUMOylation通过抑制糖解和乳酸生产来调节结直肠癌. 这种新的机制影响瘤生长,并提供了新的治疗点.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 异质核核核糖核蛋白M (hnRNPM) 是癌症中的剪接因子,但其精确的机制尚不清楚.
- 以前的研究集中在hNRNPM的RNA结合和拼接作用上.
研究的目的:
- 研究hnrnpm在结直肠癌中的非拼接作用.
- 在结直肠癌细胞中识别hnrnpm的翻译后修饰.
主要方法:
- 全球SUMO在结直肠癌细胞中的蛋白质查.
- 在 hnRNPM,SENP1 和 PFKFB3.3 之间的相互作用研究.
- 在小鼠体内瘤发生的测定.
- 对 hnRNPM SUMOylation 和相关蛋白质水平的患者样本的分析.
主要成果:
- hnRNPM 在lysine 17 中被SUMOylated,而SENP1 则介导其去SUMOylation.
- hnRNPM SUMOylation通过与PFKFB3相互作用来抑制糖解,影响其局部化和酸化,从而抑制乳酸盐的产生.
- 缺少SUMO的hNRNPM促进大肠直肠癌细胞的增殖和小鼠的瘤发生.
- 在结直肠癌患者样本中,hnRNPM SUMOylation和SENP1表达或化PFKFB3水平之间存在负相关性.
结论:
- hnRNPM SUMOylation 在调节结直肠癌细胞代谢和独立于其拼接功能的生长中发挥着关键作用.
- 调节hnnRNPM SUMOylation为结直肠癌提供了一个潜在的治疗策略.
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