MiR-130a-3p suppresses colorectal cancer growth by targeting Wnt Family Member 1 (WNT1)

Bioengineered. 2021 Dec;12(1):8407-8418. doi: 10.1080/21655979.2021.1977556.

Abstract

The microRNA miR-130a-3p (miR-130a-3p) has anti-tumor activity against numerous cancer types. Further, miR-130a-3p may target Wnt signaling, which is a critical pathway regulating tumorigenesis. Functions of miR-130a-3p in colorectal cancer (CRC) and contributions of Wnt1 pathway modulation, however, have not been examined, hence the exploration on these two aspects. In this study, in comparison with normal controls, both CRC tissue and multiple CRC cell lines showed downregulated miR-130a-3p. MiR-130a-3p overexpression contributed to a decrease in CRC cell proliferation. Additionally, its overexpression also caused reduced expression of WNT Family Member 1 (WNT1) and downstream WNT pathway factors c-myc and cyclin D1. Dual-luciferase assay revealed WNT1 as a direct target of miR-130a-3p, and further the inhibitory effect of miR-130a-3p on c-myc and cyclin D1 was proved to be reversed by overexpressed WNT1. Collectively, miR-130a-3p inhibits CRC growth by directly targeting WNT1, and miR-130a-3p and WNT1 pathway-associated factors are defined as potential targets for CRC treatment.

Keywords: Colorectal cancer; WNT1; Wnt signaling pathway; miR-130a-3p; tumor suppression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • Cyclin D1 / genetics
  • Down-Regulation*
  • Female
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Transplantation
  • Proto-Oncogene Proteins c-myc / genetics
  • Wnt1 Protein / genetics*

Substances

  • 3' Untranslated Regions
  • CCND1 protein, human
  • MIRN130 microRNA, human
  • MYC protein, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-myc
  • WNT1 protein, human
  • Wnt1 Protein
  • Cyclin D1

Grants and funding

The research was supported by Technological Innovation Major Project of Guangan City (2019SYF10).