CREB1/Lin28/miR-638/VASP Interactive Network Drives the Development of Breast Cancer

Int J Biol Sci. 2019 Oct 21;15(12):2733-2749. doi: 10.7150/ijbs.36854. eCollection 2019.

Abstract

Breast cancer is one of the most common malignant tumors worldwide. Metastasis remains the leading cause of death in breast cancer patients. Research on the mechanism of breast cancer metastasis has become a core issue in breast cancer research. Our previous series of studies have shown that VASP, as a key oncogene, plays an important role in the development of various tumors such as breast cancer. In this study, we find that miR-638 can target to inhibit VASP expression, and Lin28 acts as an RNA-binding protein to regulate the processing of miR-638, which inhibits its maturation and promotes the expression of VASP. In addition, we also find that CREB1 acts as a transcription factor that binds to the promoter of Lin28 gene and activates the Lin28/miR-638/VASP pathway. Furthermore, CREB1 can also directly bind to the promoter of VASP, and activate VASP expression, forming a CREB/Lin28/miR-638/VASP interactive network, which plays an important role in promoting cell proliferation and migration in breast cancer. Our study explained the mechanism of CREB1/Lin28/miR-638/VASP network promoting the development of breast cancer, which further elucidated the mechanism of VASP as a key oncogene, and also provided a theoretical basis for expanding new approaches to tumor biotherapy.

Keywords: CREB1; Lin28; VASP; breast cancer; cell proliferation; metastasis.; miR-638.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Proliferation
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Epidermal Growth Factor / pharmacology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / physiology*
  • Gene Knockdown Techniques
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Neoplasms, Experimental
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Prognosis
  • Protein Interaction Maps
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Wound Healing

Substances

  • Biomarkers, Tumor
  • CREB1 protein, human
  • Cell Adhesion Molecules
  • Cyclic AMP Response Element-Binding Protein
  • Lin28A protein, human
  • MIRN638 microRNA, human
  • MicroRNAs
  • Microfilament Proteins
  • Phosphoproteins
  • RNA-Binding Proteins
  • vasodilator-stimulated phosphoprotein
  • Epidermal Growth Factor