MicroRNA-8063 targets heterogeneous nuclear ribonucleoprotein AB to inhibit the self-renewal of colorectal cancer stem cells via the Wnt/β-catenin pathway

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 beta-catenin) in the Wnt/beta-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 beta-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/beta-catenin signaling to promote the self-renewal of CRCSCs.

Automated summary

This study identified miR-8063 as a tumor suppressor involved in regulating the self-renewal of CRCSCs, where loss of miR-8063 expression weakens its inhibition on hnRNPAB, leading to the activation of the Wnt/beta-catenin signaling pathway to promote CRCSCs self-renewal.