Accumulating evidence has presented that microRNA-148a/152 (miR-148a/152) acts as the tumor inhibitor in various cancers. In this article, we aimed to probe the inhibition of colon cancer stem cells by miR-148a/152 cluster via regulation of CCT6A. miR-148a/152 and CCT6A expression in colon cancer tissues and cells was detected. The relationship between miR-148a/152 expression and the clinicopathological features of patients with colon cancer was analyzed. Colon cancer stem cells (CD44+/CD133+) were selected and high/low expression of miR-148a/152 plasmids were synthesized to intervene CD44+/CD133+ colon cancer stem cells to investigate the function of miR-148a/152 in invasion, migration, proliferation, colony formation and apoptosis of cells. The growth status of nude mice was observed to verify the in-vitro results. The relationship between miR-148a/152 and CCT6A was analyzed. CCT6A upregulated and miR-148a/152 downregulated in colon cancer tissues. MiR-148a/152 expression was correlated with tumor node metastasis stage, lymph node metastasis and differentiation degree. Upregulated miR-148a/152 depressed CCT6A expression and restrained invasion and migration ability, colony formation and proliferation, induced cell apoptosis, depressed OCT4, Nanog and SOX2 mRNA expression of colon cancer stem cells, and descended tumor weight and volume in nude mice. CCT6A was a target gene of miR-148a/152. Overexpression of CCT6A protected colon cancer stem cells. Functional studies showed that upregulation of miR-148a/152 can suppress the migration, invasion and proliferation of CD44+/CD133+ colon cancer stem cells, advance its apoptosis via inhibition of CCT6A expression.

中文翻译：

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MicroRNA-148a/152簇通过调节CCT6A抑制结肠癌的肿瘤干细胞表型。

越来越多的证据表明，microRNA-148a/152 (miR-148a/152) 在多种癌症中充当肿瘤抑制剂。在本文中，我们旨在探讨 miR-148a/152 簇通过调节 CCT6A 对结肠癌干细胞的抑制作用。检测结肠癌组织和细胞中miR-148a/152和CCT6A的表达。分析miR-148a/152表达与结肠癌患者临床病理特征的关系。选取结肠癌干细胞（CD44+/CD133+），合成高/低表达miR-148a/152质粒干预CD44+/CD133+结肠癌干细胞，探讨miR-148a/152在侵袭、迁移、增殖中的功能、集落形成和细胞凋亡。观察裸鼠的生长状况以验证体外结果。分析miR-148a/152与CCT6A之间的关系。结肠癌组织中 CCT6A 上调，miR-148a/152 下调。MiR-148a/152表达与肿瘤淋巴结转移分期、淋巴结转移及分化程度相关。上调miR-148a/152可抑制CCT6A表达，抑制侵袭和迁移能力、集落形成和增殖，诱导细胞凋亡，抑制结肠癌干细胞OCT4、Nanog和SOX2 mRNA表达，并降低裸鼠肿瘤重量和体积。CCT6A 是 miR-148a/152 的靶基因。CCT6A 的过度表达可以保护结肠癌干细胞。功能研究表明，上调miR-148a/152可以抑制CD44+/CD133+结肠癌干细胞的迁移、侵袭和增殖，并通过抑制CCT6A表达促进其凋亡。