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The miR-27a/FOXJ3 Axis Dysregulates Mitochondrial Homeostasis in Colorectal Cancer Cells

Giovannina Barisciano1, Manuela Leo1, Livio Muccillo1

  • 1Department of Sciences and Technologies, University of Sannio, Via Francesco de Sanctis, 82100 Benevento, Italy.

Cancers
|October 13, 2021
PubMed

Insights

MicroRNA-27a (miR-27a) targets FOXJ3, impacting mitochondrial biogenesis and function in cancer. This axis dysregulates mitochondria, offering new therapeutic targets for tumor growth inhibition.

Area of Science:

  • Molecular Biology
  • Cancer Metabolism
  • Mitochondrial Biology

Background:

  • MicroRNA-27a (miR-27a) is implicated in regulating tumor cell metabolism.
  • Identifying novel miR-27a targets is crucial for understanding its role in cancer progression.

Purpose of the Study:

  • To identify and characterize new miR-27a targets involved in mitochondrial regulation.
  • To elucidate the functional consequences of the miR-27a/FOXJ3 axis on mitochondrial homeostasis and cancer cell behavior.

Main Methods:

  • In vitro cell models with genetic modification for miR-27a expression.
  • Validation of FOXJ3 as a direct miR-27a target.
  • Assessment of mitochondrial biogenesis, dynamics, and function (superoxide production, respiration, membrane potential) via OCR assays and confocal microscopy.
  • In vivo analysis using a mouse xenograft model.
  • Bioinformatic analysis of the TCGA-COADREAD dataset.

Main Results:

  • FOXJ3 was identified and validated as a direct target of miR-27a.
  • The miR-27a/FOXJ3 axis significantly down-modulates mitochondrial biogenesis and dysregulates mitochondrial dynamics, leading to fewer and altered organelles.
  • Cancer cells with high miR-27a/low FOXJ3 exhibited reduced mitochondrial function, including lower superoxide production, respiration, and membrane potential.
  • In vivo studies confirmed FOXJ3 as a target and indicated the axis affects mitochondrial abundance.
  • TCGA data supported an inverse correlation between FOXJ3 and miR-27a, highlighting impacts on cellular component organization and biogenesis.

Conclusions:

  • The miR-27a/FOXJ3 axis is a key regulator of mitochondrial homeostasis in cancer.
  • This axis represents a novel therapeutic target for developing strategies to inhibit tumor growth by modulating mitochondrial activity.
Keywords:
FOXJ3colorectal cancermiRNAmitochondriatumor metabolism

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