The presence of cancer stem cells (CSCs) is a major cause of therapeutic failure in a variety of cancer types, including colorectal cancer (CRC). However, the underlying mechanisms that regulate the self‑renewal of colorectal cancer stem cells (CRCSCs) remain unclear. Our previous study utilized CRCSCs and their parent cells; through gene microarray screening and bioinformatics analysis, we hypothesized that microRNA (miR)‑8063 may bind to, and regulate the expression of, heterogeneous nuclear ribonucleoprotein AB (hnRNPAB) to facilitate the regulation of CRCSC self‑renewal. The aim of the present study was to confirm this conjecture through relevant experiments. The results indicated that compared with that in parent cells, miR‑8063 expression was significantly downregulated in CRCSCs, while hnRNPAB expression was increased. Furthermore, hnRNPAB was identified as a direct target of miR‑8063 using a dual‑Luciferase assay. Overexpression of hnRNPAB promoted the acquisition of CSC characteristics in CRC cells (increased colony formation ability, enhanced tumorigenicity, and upregulated expression of CSC markers), as well as the upregulation of key proteins (Wnt3a, Wnt5a and β‑catenin) in the Wnt/β‑catenin signaling pathway. Similarly, after silencing miR‑8063 in CRC cells, the characteristics of CSC were altered, and the expression of hnRNPAB protein was promoted. However, post overexpression of miR‑8063 in CRCSCs, the self‑renewal ability of CSCs was weakened with the downregulation of hnRNPAB protein, Wnt3a, Wnt5a and β‑catenin. These results suggest that as a tumor suppressor, miR‑8063 is involved in regulating the self‑renewal of CRCSCs, where loss of miR‑8063 expression weakens its inhibition on hnRNPAB, which leads to the activation of Wnt/β‑catenin signaling to promote the self‑renewal of CRCSCs.

中文翻译：

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MicroRNA-8063 靶向异质核糖核蛋白 AB，通过 Wnt/β-catenin 通路抑制结直肠癌干细胞的自我更新。

癌症干细胞 (CSC) 的存在是导致包括结直肠癌 (CRC) 在内的多种癌症类型治疗失败的主要原因。然而，调节结直肠癌干细胞（CRCSCs）自我更新的潜在机制仍不清楚。我们之前的研究利用了 CRCSCs 及其母细胞；通过基因芯片筛选和生物信息学分析，我们假设 microRNA (miR)-8063 可能结合并调节异质核糖核蛋白 AB (hnRNPAB) 的表达，从而促进 CRCSC 自我更新的调节。本研究的目的是通过相关实验证实这一猜想。结果表明，与亲本细胞相比，CRCSCs中miR-8063表达显着下调，而hnRNPAB表达增加。此外，使用双荧光素酶测定法将 hnRNPAB 鉴定为 miR-8063 的直接靶标。hnRNPAB 的过表达促进了 CRC 细胞中 CSC 特征的获得（集落形成能力增强、致瘤性增强、CSC 标志物表达上调），以及 Wnt/ β-catenin 信号通路。同样，在CRC细胞中沉默miR-8063后，CSC的特征发生改变，hnRNPAB蛋白的表达得到促进。然而，miR-8063在CRCSCs中过表达后，随着hnRNPAB蛋白、Wnt3a、Wnt5a和β-catenin的下调，CSCs的自我更新能力减弱。这些结果表明，作为肿瘤抑制因子，miR-8063 参与调节 CRCSCs 的自我更新，