Department of Anorectal Surgery, Xinxiang Central Hospital General Surgery III, Xinxiang City, Henan, China.
Anticancer Drugs. 2022 Jan 1;33(1):e610-e621. doi: 10.1097/CAD.0000000000001198.
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.
越来越多的证据表明，microRNA-148a/152（miR-148a/152）在多种癌症中作为肿瘤抑制剂发挥作用。本文旨在通过调控 CCT6A 来探究 miR-148a/152 簇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。选择 CD44+/CD133+结肠癌细胞，合成高/低表达 miR-148a/152 质粒，干预 CD44+/CD133+结肠癌细胞，探讨 miR-148a/152 对细胞侵袭、迁移、增殖、集落形成和凋亡的作用。观察裸鼠的生长状况，验证体外结果。分析 miR-148a/152 与 CCT6A 的关系。结肠癌组织中 CCT6A 上调，miR-148a/152 下调。miR-148a/152 的表达与肿瘤淋巴结转移分期、淋巴结转移和分化程度相关。上调的 miR-148a/152 抑制 CCT6A 的表达，抑制侵袭和迁移能力、集落形成和增殖，诱导细胞凋亡，下调结肠癌干细胞中 OCT4、Nanog 和 SOX2mRNA 的表达，降低裸鼠肿瘤的重量和体积。CCT6A 是 miR-148a/152 的靶基因。过表达 CCT6A 可保护结肠癌干细胞。功能研究表明，上调 miR-148a/152 可通过抑制 CCT6A 的表达来抑制 CD44+/CD133+结肠癌细胞的迁移、侵袭和增殖，促进其凋亡。
