多梳家族因子1对结直肠癌干细胞富集的影响及其机制

姬光瑜; 周娟; 李心悦; 郝洪波

doi:10.16098/j.issn.0529-1356.2022.05.011

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解剖学报 ›› 2022, Vol. 53 ›› Issue (5) : 613-619. DOI: 10.16098/j.issn.0529-1356.2022.05.011

多梳家族因子1对结直肠癌干细胞富集的影响及其机制

姬光瑜¹周娟¹ 李心悦¹ 郝洪波^2*

作者信息 +

Effect of polycomb group facor 1 on the enrichment of colorectal cancer stem cells and its mechanism

JI Guang-yu¹ ZHOU Juan¹ LI Xin-yue¹ HAO Hong-bo^2*

Author information +

文章历史 +

摘要

目的探讨表观遗传调控因子多梳家族因子1（PCGF1）对结直肠癌干细胞富集的影响以及相关的调控机制。方法通过数据库分析PCGF1在结直肠癌肿瘤组织中的表达，采用Real-time PCR技术检测PCGF1在结直肠癌肿瘤细胞以及正常肠上皮细胞中的表达。构建PCGF1稳定敲低的结直肠癌细胞系，采用肿瘤成球实验分析PCGF1对结直肠癌干细胞富集的影响。通过Oncomine和GEPIA数据库、Real-time PCR以及Western blotting实验检测PCGF1对干性相关标记物以及干细胞自我更新相关信号通路Wnt、Notch通路中关键蛋白的影响。结果 PCGF1在结直肠癌肿瘤组织与细胞中的表达明显高于其对应的癌旁组织与正常肠上皮细胞。PCGF1敲低导致结直肠癌干细胞的成球能力减弱，干性相关标记物表达降低。PCGF1的表达与干细胞自我更新相关信号通路Wnt、Notch通路中关键蛋白之间成正向相关性，敲低PCGF1降低Wnt信号通路β连环蛋白（β-catenin）的表达。结论 PCGF1影响结直肠癌干细胞的富集并正向调控结直肠癌干细胞自我更新相关信号通路中关键蛋白的表达。

Abstract

Objective To explore the effect of epigenetic regulator polycomb group factor 1(PCGF1) on the enrichment of colorectal cancer stem cells and its mechanism. Methods Meta-analysis was used to predict the expression of PCGF1 in normal and colorectal cancer tissues. The gene expression of PCGF1 in colorectal cancer tumor cells and normal intestinal epithelium cells was detected by Real-time PCR. PCGF1 loss-of-function subclone was generated in HCT116, and stemness was evaluated by spheroid formation. The effects of PCGF1 on stemness markers and the key proteins in Wnt and Notch pathways were detected by Oncomine and GEPIA database, Realtime PCR and Western blotting. Results PCGF1 was markedly upregulated in colorectal cancer cells and tissues. PCGF1 knockdown strongly inhibited tumor sphere formation of HCT116 and stemness markers expression. There was a positive correlation between PCGF1 and the key proteins in Wnt and Notch pathways. PCGF1 knockdown reduced the expression of β-catenin in Wnt signaling pathway. Conclusion PCGF1 affects the enrichment of colorectal cancer stem cells and regulates the expression of key proteins in the signal pathway which is related to colorectal cancer stem cells self-renewal.

导出引用

姬光瑜周娟李心悦郝洪波. 多梳家族因子1对结直肠癌干细胞富集的影响及其机制[J]. 解剖学报. 2022, 53(5): 613-619 https://doi.org/10.16098/j.issn.0529-1356.2022.05.011

JI Guang-yu ZHOU Juan LI Xin-yue HAO Hong-bo. Effect of polycomb group facor 1 on the enrichment of colorectal cancer stem cells and its mechanism[J]. Acta Anatomica Sinica. 2022, 53(5): 613-619 https://doi.org/10.16098/j.issn.0529-1356.2022.05.011

中图分类号： R735.3

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