AGO2-RIP-Seq reveals miR-34/miR-449 cluster targetome in sinonasal cancers

PLoS One. 2024 Jan 12;19(1):e0295997. doi: 10.1371/journal.pone.0295997. eCollection 2024.

Abstract

Sinonasal tumours are heterogeneous malignancies, presenting different histological features and clinical behaviour. Many studies emphasize the role of specific miRNA in the development and progression of cancer, and their expression profiles could be used as prognostic biomarkers to predict the survival. Recently, using the next-generation sequencing (NGS)-based miRNome analysis the miR-34/miR-449 cluster was identified as miRNA superfamily involved in the pathogenesis of sinonasal cancers (SNCs). In the present study, we established an Argonaute-2 (AGO2): mRNA immunoprecipitation followed by high-throughput sequencing to analyse the regulatory role of miR-34/miR-449 in SNCs. Using this approach, we identified direct target genes (targetome), which were involved in regulation of RNA-DNA metabolic, transcript and epigenetic processes. In particular, the STK3, C9orf78 and STRN3 genes were the direct targets of both miR-34c and miR-449a, and their regulation are predictive of tumour progression. This study provides the first evidence that miR-34/miR-449 and their targets are deregulated in SNCs and could be proposed as valuable prognostic biomarkers.

MeSH terms

  • Argonaute Proteins* / genetics
  • Argonaute Proteins* / metabolism
  • Biomarkers
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Neoplasms* / genetics
  • Paranasal Sinuses / pathology

Substances

  • AGO2 protein, human
  • Argonaute Proteins
  • Biomarkers
  • MicroRNAs
  • MIRN34 microRNA, human
  • MIRN449 microRNA, human

Grants and funding

The study was supported by grant of the Polytechnic University of Marche no. PSA-2017- 040020-R. SCIENT.A-2018. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."