在OSCC细胞中,IRF2BP2通过提高线粒体裂变依赖的脂肪酸氧化率来驱动OSCC细胞的淋巴转移
Xin Pang1, Tian-Jiao Li1, Rong-Jia Shi1
1Department of Oral and Maxillofacial Surgery, State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Molecular carcinogenesis
|September 22, 2023
概括
干扰素调节因子2结合蛋白2 (IRF2BP2) 通过增强脂肪酸氧化和线粒体裂变,促进口腔癌转移. 向IRF2BP2可能为带有淋巴结转移的口腔状细胞癌提供一种新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 淋巴结转移 (LNM) 是口腔状细胞癌 (OSCC) 预后的一个关键因素.
- 干扰素调节因子2结合蛋白2 (IRF2BP2) 在LNM的OSCC中的作用仍未得到研究.
研究的目的:
- 研究IRF2BP2在OSCC转移中的作用,特别关注LNM.
- 阐明涉及脂肪酸氧化 (FAO) 和线粒体动态的潜在分子机制.
主要方法:
- 免疫组织化学和RT-PCR用于OSCC组织中IRF2BP2表达分析.
- 试验室功能丧失和救援试验以评估入侵,淋巴入侵和上皮-介质细胞过渡 (EMT).
- 显微镜技术 (共聚焦,传输电子) 和西布洛特用于研究线粒体裂变和粮农组织.
- 在体内瘤模型中评估IRF2BP2在瘤生长和LNM中的作用.
主要成果:
- 在OSCC中,IRF2BP2过度表达与LNM相关.
- 通过IRF2BP2敲击抑制了OSCC细胞入侵,淋巴细胞入侵和EMT,同时通过CPT1A下调减少了FAO.
- IRF2BP2通过增强Drp1酸化和线粒体局部化来促进线粒体裂变,提高CPT1A和FAO的调节.
- 在体内,IRF2BP2倒置显著抑制了瘤生长和LNM.
结论:
- 通过激活线粒体裂变和通过CPT1A升级粮农组织,IRF2BP2促进OSCC LNM.
- 针对IRF2BP2-FAO途径为LNM阳性OSCC提供了一个潜在的治疗策略.
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