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

Abstract

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.

Dexmedetomidine protects H9C2 rat cardiomyocytes against hypoxia/reoxygenation injury by regulating the long non-coding RNA colon cancer-associated transcript 1/microRNA-8063/Wnt/β-catenin axis

“…In addition, our study showed that CCAT1 knockdown activated the Wnt/β-catenin signaling pathway, which was inhibited by miR-8063 interference. These result are contrary to the previously reported roles of CCAT1 and miR-8063 in cancer [ 42 , 43 ]. We suspect that this is due to differences in the disease.…”

Cancer Stem Cells and Their Vesicles, Together with Other Stem and Non-Stem Cells, Govern Critical Cancer Processes: Perspectives for Medical Development

“…The main role of EVs also includes their fusion with macrophages and other immune cells [ 30 , 31 ]. CSCs and their EVs are able to modulate cancer cell proliferation by the release of proteins [ 44 , 45 , 46 ] and miRNAs [ 30 , 47 , 48 , 49 , 50 , 51 ]. Examples are increasing, with results in favor or against cancer.…”

“…The miR-92/PD-L1 pathway contributes to the suppression of immune cell function [ 30 ] and miR-200c stimulates the metastatic traits in colorectal cancer [ 47 ]. On the other hand, human liver cancer is attenuated in vitro and in vivo by miR-145 and miR-200 [ 48 ]; inhibition of lung metastasis is induced in osteosarcoma by miR-101 [ 49 ]; miR-8063 inhibits self renewal of GSC [ 50 ]; miR-663 inhibits the CSCs of a glioma [ 51 ]; and miR-1468-5p promotes a tumor immune escape [ 52 ]. Interestingly, many of the effects reported in this section, induced by CSCs and miRs, are mediated by the activation of various signaling pathways such AKT [ 22 , 46 ], GSK3-β [ 22 ], Wnt/β-catenin [ 22 , 23 , 50 , 51 ], and TGF-β/SMAD [ 53 ].…”

“…The cancer role of MSCs has also been investigated via molecules (proteins, lipids, miRNAs), most often released from the EV cargoes. Identification of miRNAs active at one or more steps of MSC signaling cascades [ 59 , 60 , 61 , 62 ], and which are different from those involved in CSC action [ 47 , 48 , 49 , 50 , 51 ] were already established some years ago. Recent findings have led to the identification not only of miRs but also of signaling cascades they contribute to in order to activate.…”

Long noncoding RNA PPP1R14B-AS1 imitates microRNA-134-3p to facilitate breast cancer progression by upregulating LIM and SH3 protein 1

“…By searching miRDB, 15 miRNAs were predicted to possess potential binding sites for PPP1R14B-AS1 (Table 1). Among these candidates, miR-134-3p [28], miR-8063 [29], miR-3135b [30], miR-765 [31], miR-4269 [32], miR-3168 [33] and miR-11181-3p [34] were reported to contribute to carcinogenesis and cancer progression; thus, they were chosen for further verification. Afterward, qRT-PCR was conducted to quantify these miRNAs in si-PPP1R14B-AS1-transfected breast cancer cells.…”