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Suppression of mTOR Signaling by miR-302/367 Cluster in Breast Cancer Cells

Mahsa Alemi1, Masoumeh Fakhr Taha1, Arezoo Bazargani1

  • 1Department of Stem Cells and Regenerative Medicine, Institute for Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|August 16, 2025
PubMed

Insights

The miR-302/367 cluster suppresses tumors by inhibiting the mTOR pathway in breast cancer cells. This microRNA cluster targets key mTOR regulators, reducing their expression and slowing cancer cell growth.

Area of Science:

  • Molecular biology
  • Cancer research
  • Biochemistry

Background:

  • The mechanistic target of rapamycin (mTOR) signaling pathway regulates critical cellular processes like protein synthesis and metabolism.
  • Aberrant mTOR signaling is frequently observed in various cancers.
  • The miR-302/367 microRNA cluster has demonstrated tumor-suppressive properties.

Purpose of the Study:

  • To investigate the impact of miR-302/367 cluster overexpression on mTOR signaling in cancer cells.
  • To identify and validate direct targets of miR-302/367 within the mTOR pathway.
  • To elucidate the molecular mechanisms underlying the tumor-suppressive effects of miR-302/367.

Main Methods:

  • Bioinformatic analysis to predict miR-302/367 targets in the mTOR pathway.
  • Dual-luciferase reporter assays to confirm direct targeting of PIK3CB, RRAGD, and FNIP1.
  • Gene and protein expression analysis in breast cancer cell lines (SK-BR-3, MDA-MB-231) after miR-302/367 transfection.
  • Cell proliferation assays.

Main Results:

  • PIK3CB, RRAGD, and FNIP1 were validated as direct targets of the miR-302/367 cluster.
  • Overexpression of miR-302/367 led to decreased transcript and protein levels of PIK3CB, RRAGD, and FNIP1.
  • miR-302/367 transfection inhibited breast cancer cell proliferation.
  • Downregulation of multiple mTOR pathway components was observed, indicating a broad inhibitory effect.

Conclusions:

  • The miR-302/367 cluster exerts tumor-suppressive effects in breast cancer by modulating mTOR signaling at multiple levels.
  • This microRNA cluster directly targets key components of the mTOR pathway, including PIK3CB, RRAGD, and FNIP1.
  • The findings suggest therapeutic potential for the miR-302/367 cluster in cancer treatment.
Keywords:
breastcancermTORmiR‐302/367

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