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通过调节ABCA1转录,PGC-1α促进结直肠癌转移

Wei Chen¹, Qiushuang Zhang¹, Xiaoshuo Dai¹

¹Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province, 450001, P. R. China.

|July 3, 2023

概括

高PGC-1α表达促进结直肠癌 (CRC) 转移,通过通过ABCA1.1.调节胆固醇外流来调节胆固醇外流. 使用异基因因抑制这种途径为CRC提供了潜在的治疗策略.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
生物化学生物化学

背景情况:

结肠直肠癌 (CRC) 转移是一个重大挑战,其潜在机制需要进一步阐明.
氧酶增殖器激活受体玛协活性剂1α (PGC-1α),一个线粒体调节器,在癌症中起着复杂的作用.
了解PGC-1α在CRC转移中的作用对于开发向疗法至关重要.

研究的目的:

研究PGC-1α在结直肠癌进展和转移中的作用.
阐明PGC-1α影响CRC转移的分子机制.
为了确定抑制PGC-1α驱动的CRC转移的潜在治疗标.

主要方法:

在CRC组织中分析PGC-1α表达和与转移状态的相关性.
在体外和体内实验涉及PGC-1α的淘汰,以评估其对CRC生长和转移的影响.
转录组分析以确定PGC-1α调节通路.
研究PGC-1α,YY1和ABCA1.1.之间的相互作用.
评估异基原蛋白 (ISL) 作为PGC-1α诱导的CRC转移的抑制剂.

主要成果:

在CRC组织中PGC-1α的表达很高,并且与淋巴结和肝脏转移具有积极的相关性.
在实验室和体内,PGC-1α倒置显著抑制了CRC生长和转移.
发现PGC-1α调节了ATP结合盒载体1 (ABCA1) 介导的胆固醇外流.
PGC-1α与YY1相互作用,促进ABCA1转录,导致胆固醇流量增加和表皮转介质转变 (EMT) 驱动的转移.
这种天然化合物isoliquiritigenin (ISL) 有效抑制了ABCA1并减少了PGC-1α诱导的CRC转移.

结论:

PGC-1α通过增强ABCA1介导的胆固醇流量和驱动EMT来促进结直肠癌转移.
PGC-1α/YY1/ABCA1轴代表了一种促进CRC转移的新机制.
伊索利基基因因显示出作为治疗剂的承诺,通过抑制ABCA1.1,以准PGC-1α驱动的CRC转移.

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