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ErbB4-encoded novel miRNAs act as tumor suppressors by regulating ErbB/PI3K signaling

Zahra Ghaemi1, Bahram M Soltani1, Seyed Javad Mowla1

  • 1Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
|November 28, 2022
PubMed
Abstract

Insights

Novel tumor suppressor microRNAs, ErbB4-miR1/2, were identified and found to attenuate ErbB/PI3K signaling. These microRNAs are downregulated in breast and colon cancers, suppressing tumor progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • ErbB/PI3K signaling is crucial in cancer development.
  • MicroRNAs (miRNAs) are key regulators of this pathway.

Purpose of the Study:

  • Identify novel miRNAs associated with ErbB loci.
  • Investigate the functional role of these miRNAs in ErbB/PI3K signaling and cancer progression.

Main Methods:

  • Bioinformatics and RNA-seq for miRNA discovery in breast and colon cancer cells.
  • RT-qPCR, Western blotting, and dual-luciferase assays for mechanism elucidation.
  • Functional assays (proliferation, viability, migration, ROS) to assess miRNA effects.

Main Results:

  • Identified ErbB4-miR1/2 as novel miRNAs encoded by the ErbB4 gene.
  • Found ErbB4-miR1/2 downregulated in tumor tissues and cancer cells.
  • Demonstrated ErbB4-miR1/2 regulate ErbB2/ErbB3 and suppress ErbB/PI3K signaling (decreased p-AKT/AKT).
  • Overexpression of ErbB4-miR1/2 inhibited proliferation, viability, migration, and increased ROS production.

Conclusions:

  • ErbB4-miR1/2 are novel tumor suppressor miRNAs.
  • These miRNAs attenuate ErbB/PI3K signaling in breast and colon cancer cells.
Keywords:
ErbB/PI3K signalingErbB4-miR1/2MicroRNAcancertumor suppressor

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