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MiR-644a Disrupts Oncogenic Transformation and Warburg Effect by Direct Modulation of Multiple Genes of

Jey S Ebron1,2, Eswar Shankar3, Jagjit Singh1,2

  • 1Department of Biological Sciences, Cleveland State University, Cleveland, Ohio.

Cancer Research
|February 28, 2019
PubMed

Insights

MicroRNA-644a (miR-644a) downregulation promotes castration-resistant prostate cancer (CRPC) by affecting androgen signaling, metabolism, and EMT. Restoring miR-644a potentiates enzalutamide therapy in CRPC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Castration-resistant prostate cancer (CRPC) is characterized by a heterogeneous tumor microenvironment.
  • Key cellular mechanisms include dysregulated androgen signaling, aerobic glycolysis (Warburg effect), and aberrant transcription factor activation (AR, c-Myc).

Purpose of the Study:

  • To investigate the role of miR-644a in CRPC pathogenesis and its potential to enhance enzalutamide therapy.
  • To elucidate the molecular mechanisms by which miR-644a influences the tumor microenvironment.

Main Methods:

  • Utilized in vitro, in vivo, and animal models of CRPC.
  • Performed RNA sequencing analysis on tumor xenografts.
  • Investigated the direct targeting of oncogenic factors by miR-644a.

Main Results:

  • Downregulation of miR-644a correlated with dysregulated cellular processes in CRPC.
  • MiR-644a suppressed c-Myc, AR coregulators, Bcl-xl, Bcl2, ZEB1, cdk6, Snail, Akt, IGF1R, and GAPDH.
  • MiR-644a suppressed the Warburg effect and modulated epithelial-mesenchymal transition (EMT).
  • RNA sequencing confirmed downregulation of these factors in animal models.

Conclusions:

  • MiR-644a plays a critical role in fine-tuning oncogenesis within the CRPC tumor microenvironment.
  • Therapeutic restoration of miR-644a can suppress key oncogenic pathways.
  • MiR-644a potentiates the efficacy of enzalutamide therapy in CRPC patients.

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