沉默PCCA通过调节EMT和M1巨细胞极化抑制CRC生长和扩散
Chuyi Zhang1,2,3, Zhinan Zheng1,2, Huaiming Wang2,4
1Department of Anaesthesia, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
International journal of medical sciences
|January 2, 2025
概括
propionyl-CoA 碳素酶α链 (PCCA) 促进结直肠癌 (CRC) 的进展和转移. 抑制PCCA可以减少CRC细胞的入侵,生长和扩散,这表明PCCA是CRC治疗的潜在治疗标.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症转移研究 癌症转移研究
背景情况:
- 结肠直肠癌 (CRC) 的进展和转移由于治疗目标有限,造成了重大临床挑战.
- 初步发现表明,propionyl-CoA carboxylase alpha chain (PCCA) 基因在CRC中被上调,需要对其功能作用进行研究.
研究的目的:
- 为了研究尼尔-CoA碳素酶α链 (PCCA) 在结直肠癌 (CRC) 进展和转移中的功能性作用.
- 确定PCCA是否可以作为CRC的潜在治疗点.
主要方法:
- 利用生物信息学分析,人类结直肠瘤组织和CRC细胞系来评估PCCA表达.
- 采用伤口愈合,Transwell,CCK-8试验,西式抹杀,小鼠模型,流细胞计和定量PCR来评估PCCA对CRC细胞行为的影响,瘤生长,转移和巨细胞两极分化.
主要成果:
- 在CRC组织中PCCA的高表达与预后不佳相关. 通过PCCA的淘汰,显著减少了CRC细胞的迁移,入侵和增殖.
- 抑制PCCA导致表皮细胞-介质细胞过渡 (EMT) 逆转,ERK/GSK3β通路的失活,并抑制瘤生长和肺转移.
- 击败PCCA促进了瘤微环境中的M1-巨细胞两极分化.
结论:
- 通过逆转EMT,不激活ERK/GSK3β通路,并促进M1-巨细胞两极分化,PCCA Knockdown有效地抑制结直肠癌的进展和转移.
- 现在,PCCA成为控制结直肠癌进展和转移的有希望的治疗标.
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