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

Oncol Rep. 2021 Oct;46(4):219. doi: 10.3892/or.2021.8170. Epub 2021 Aug 13.

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.

Keywords: Wnt/β‑catenin signaling pathway; colorectal cancer; heterogeneous nuclear ribonucleoprotein AB; microRNA‑8063; self‑renewal.

MeSH terms

  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Down-Regulation
  • HT29 Cells
  • Heterogeneous-Nuclear Ribonucleoproteins / genetics*
  • Heterogeneous-Nuclear Ribonucleoproteins / metabolism
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplastic Stem Cells / metabolism*
  • Up-Regulation
  • Wnt Signaling Pathway / genetics*
  • beta Catenin / genetics*
  • beta Catenin / metabolism

Substances

  • Heterogeneous-Nuclear Ribonucleoproteins
  • MicroRNAs
  • beta Catenin

Grants and funding

The present study was supported by the National Natural Science Foundation of China (grant no. 81560404), the Science and Technology Fund Foundation of Guizhou (grant no. [2017]5733-053), the Science and Technology Fund Foundation of Zunyi City (grant no. [2019]69) and the Fund Foundation of Guizhou Health Committee (grant no. gzwjkj2019-1-122).