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MiR-449a antagonizes EMT through IL-6-mediated trans-signaling in laryngeal squamous cancer

Alessia Maria Cossu1,2, Federica Melisi1,2, Teresa Maria Rosaria Noviello2,3

  • 1Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.

Molecular Therapy. Nucleic Acids
|March 1, 2024
PubMed

Insights

MicroRNAs (miRNAs) are crucial in cancer. This study shows reduced miR-449a levels in laryngeal squamous cell carcinoma (LSCC) patients with metastases, suggesting miR-449a suppresses LSCC spread.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • MicroRNAs (miRNAs) regulate gene expression and are implicated in cancer progression.
  • miRNAs represent potential therapeutic targets and biomarkers for cancer treatment.

Purpose of the Study:

  • To investigate the role of specific miRNAs and their target genes in laryngeal squamous cell carcinoma (LSCC) development.
  • To determine if miR-449a influences LSCC metastasis.

Main Methods:

  • Analysis of miR-449a levels in LSCC patients with and without nodal metastases.
  • Identification of miR-449a targets using AmpliSeq Transcriptome in transfected cell lines.
  • Assessment of IL-6 trans-signaling pathway activity, cell invasion, and migration in vitro and in vivo.

Main Results:

  • A significant decrease in miR-449a was observed in LSCC patients with nodal metastases.
  • IL6-R was identified as a potential target of miR-449a.
  • Downregulation of IL6-R and reduced downstream signaling inhibited the IL-6 trans-signaling pathway, suppressing LSCC cell invasion and migration.

Conclusions:

  • miR-449a suppresses LSCC metastatization by inhibiting the IL-6 trans-signaling pathway.
  • miR-449a affects cellular sensitivity to pro-inflammatory stimuli.
  • These findings highlight miR-449a as a potential biomarker and therapeutic target for LSCC.
Keywords:
IL-6 trans-signalingLSCCMT: non-coding RNAsgene expressionmetastases miR-449amicroRNAs

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