HER2-intronic miR-4728-5p facilitates HER2 expression and accelerates cell proliferation and migration by targeting EBP1 in breast cancer

PLoS One. 2021 Feb 2;16(2):e0245832. doi: 10.1371/journal.pone.0245832. eCollection 2021.

Abstract

HER2 amplification greatly contributes to the tumorigenesis of multiple cancers. Intronic miR-4728-5p is transcribed along with its host gene HER2. However, little is known about the role of miR-4728-5p in cancer. This study aims to elucidate the potential role of miR-4728-5p and the underlying mechanism in breast cancer. Kaplan-Meier analysis showed that higher expression of HER2 led to worse survival outcomes in breast cancer patients. The TCGA dataset revealed that compared to normal breast tissues, HER2 and miR-4728-5p levels were significantly upregulated in breast cancer tissues with a positive correlation. In functional assays, miR-4728-5p was confirmed to promote the proliferation and migration in breast cancer cell BT474. EBP1 was identified as a direct target of miR-4728-5p via bioinformatics and luciferase reporter assays. miR-4728-5p was further demonstrated to increase HER2 expression and promote cell proliferation and migration by directly inhibiting EBP1 in breast cancer. Taken together, the HER2-intronic miR-4728-5p/EBP1/HER2 feedback loop plays an important role in promoting breast cancer cell proliferation and migration. Our study provides novel insights for targeted therapies of breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics
  • Down-Regulation / genetics
  • Humans
  • Introns / genetics*
  • Kaplan-Meier Estimate
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • RNA-Binding Proteins / genetics*
  • Receptor, ErbB-2 / genetics*

Substances

  • Adaptor Proteins, Signal Transducing
  • MIRN4728 microRNA, human
  • MicroRNAs
  • PA2G4 protein, human
  • RNA-Binding Proteins
  • ERBB2 protein, human
  • Receptor, ErbB-2

Grants and funding

This study was supported by the following funders: the Chinese Science and Technology Major Project of China, 2015ZX09102023-003, received by CZ; the China Postdoctoral Science Foundation, No. 2018M642211, received by ML; the National Natural Science Foundation of China, 81602697, received by ZZ; the National Natural Science Foundation of China, 31601057, received by CW.