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Updated: Oct 21, 2025

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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A computational approach on studying the regulation of TGF-β1-stimulated Runx2 expression by MicroRNAs in human

S Pranavkrishna1, G Sanjeev1, R L Akshaya1

  • 1Department of Biotechnology, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, 603 103, Tamil Nadu, India.

Computers in Biology and Medicine
|September 7, 2021
PubMed
Abstract

Insights

Transforming growth factor-beta1 (TGF-β1) loss in breast cancer promotes metastasis. This study identifies miR-5703 as a key regulator of runt-related transcription factor 2 (Runx2), offering potential therapeutic targets for bone metastasis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Transforming growth factor-beta1 (TGF-β1) normally inhibits epithelial cell growth.
  • Loss of TGF-β1 in breast cancer correlates with increased invasion and osteolytic bone metastasis, partly driven by runt-related transcription factor 2 (Runx2).
  • Non-coding RNAs, including microRNAs (miRNAs), are known regulators of Runx2 in various conditions.

Purpose of the Study:

  • To identify specific miRNAs targeting Runx2.
  • To investigate the role of miR-5703 in regulating Runx2 activity in breast cancer cells.
  • To explore the potential of miR-5703 as a biomarker or therapeutic agent for breast cancer bone metastasis.

Main Methods:

  • Bioinformatics tools (miRDB, STarMir, Venny, TarBase) were used to predict miRNAs targeting Runx2.
  • RT-qPCR was employed to analyze the expression of precursor and mature miRNAs.
  • Computational analyses (TransmiR, bc-GenExMiner v4.6) were performed to identify indirect regulatory networks of Runx2.

Main Results:

  • Thirteen miRNAs predicted to target Runx2 were identified.
  • miR-5703 expression was significantly downregulated in human breast cancer cells treated with TGF-β1.
  • miR-5703 was computationally predicted to indirectly regulate Runx2 by affecting signaling pathways like Jak/Stat, MAPK, and Wnt/β-Catenin.
  • Expression profiles of Runx2 and related genes correlated with miR-5703 in triple-negative breast cancer patients.

Conclusions:

  • The identification of miR-5703 and its regulatory network for Runx2 provides insights into breast cancer bone metastasis.
  • This discovery may lead to the development of novel miRNA-based biomarkers and therapeutics for cancer treatment.
Keywords:
Breast cancerOsteolytic metastasisRunx2Signaling cascademiRNAs

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