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Regulation of the Key Epithelial Cancer Suppressor miR-124 Function by Competing Endogenous RNAs

Eleonora A Braga1,2, Marina V Fridman3, Alexey M Burdennyy1

  • 1Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia.

International Journal of Molecular Sciences
|November 11, 2022
PubMed

Insights

MicroRNA-124 (miR-124) acts as a tumor suppressor by inhibiting oncogenic proteins in epithelial cancers. Its dysregulation involves epigenetic changes and interactions with long non-coding RNAs and circular RNAs, offering therapeutic potential.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • MicroRNA-124 (miR-124) expression is decreased in various epithelial cancers, where it functions as a tumor suppressor.
  • miR-124 inhibits the translation of multiple oncogenic proteins, playing a critical role in cancer progression.

Purpose of the Study:

  • To investigate the regulatory mechanisms of miR-124 expression in epithelial cancers.
  • To explore the role of competing endogenous RNAs (ceRNAs) involving long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in miR-124-mediated cancer pathways.
  • To identify potential therapeutic targets based on miR-124 interactions.

Main Methods:

  • Bioinformatic analysis and literature review to identify lncRNA/miR-124/mRNA and circRNA/miR-124/mRNA interactions (ceRNA networks).
  • Analysis of identified axes for involvement in cancer hallmarks like epithelial-mesenchymal transition (EMT), metastasis, signaling pathways, and patient outcomes.
  • Review of studies detailing miR-124 regulation by circRNAs, including circHIPK3.

Main Results:

  • Epigenetic mechanisms, including gene hypermethylation and ceRNA networks, significantly regulate miR-124 expression.
  • Over 40 lncRNA/miR-124/mRNA interactomes were identified, with MALAT1, NEAT1, HOXA11-AS, and XIST being prominent.
  • Specific axes are linked to EMT, metastasis, key cancer signaling pathways (Wnt/β-catenin, TGF-β, etc.), stemness, impaired survival, and chemoresistance.
  • 14 circRNA regulations of miR-124 were found, with circHIPK3 implicated in proliferation, EMT, and drug resistance.

Conclusions:

  • Dysregulation of miR-124, influenced by epigenetic factors and complex ceRNA networks, is crucial in epithelial cancers.
  • Identified miR-124 interacting partners and pathways represent promising therapeutic targets for cancer treatment.
  • Further research into miR-124-based therapies holds significant potential for improving patient outcomes.
Keywords:
EMTchemoresistancecircRNAepigenetic mechanismsepithelial cancerslncRNAmetastasismiR-124signaling pathways

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