MicroRNA-488 inhibits proliferation and motility of tumor cells via downregulating FSCN1, modulated by Notch3 in breast carcinomas

Cell Death Dis. 2020 Oct 24;11(10):912. doi: 10.1038/s41419-020-03121-5.

Abstract

As important modulators in multiple physiological processes, microRNAs (miRNAs) have been reported in various malignant tumors, including breast cancer. The current study investigated the function of a new tumor suppressor microRNA, miR-488, and its molecular mechanism of metastasis in breast cancers. CCK8 and transwell assays revealed that the upregulated miR-488 level significantly inhibited the proliferation and migration of breast cancer cells. As a potential downstream gene, the mRNA and protein level of FSCN1 was suppressed by increased miR-488 and vice versa. Luciferase assay showed that miR-488 directly bind to the 3'UTR of FSCN1 and suppressed the translation process of FSCN1. The promoter region of miR-488 was directly bound by Notch3 and promoted the expression of miR-488 transcriptionally. Immunohistochemistry results revealed that in patients with breast cancer, the expression of Notch3 and were negatively correlated with the FSCN1 levels significantly. Therefore, the current finding predicted miR-488 as a tumor suppressor molecule in breast cancer, and demonstrated that Notch3/miR-488/FSCN1 axis is established and involved in regulating the metastasis of breast cancers, providing novel therapeutic targets for patients with breast cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Down-Regulation
  • Female
  • Humans
  • MCF-7 Cells
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Receptor, Notch3 / genetics
  • Receptor, Notch3 / metabolism*
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology

Substances

  • Carrier Proteins
  • FSCN1 protein, human
  • MIRN488 microRNA, human
  • MicroRNAs
  • Microfilament Proteins
  • NOTCH3 protein, human
  • Receptor, Notch3