The contribution of micrornas to the inflammatory and neoplastic characteristics of erdheim–chester disease

Ran Weissman, Eli L. Diamond, Julien Haroche, Nir Pillar, Guy Shapira, Benjamin H. Durham, Justin Buthorn, Fleur Cohen, Michelle Ki, Galia Stemer, Gary A. Ulaner, Zahir Amoura, Jean François Emile, Roei D. Mazor, Noam Shomron, Omar I. Abdel-Wahab, Ofer Shpilberg, Oshrat Hershkovitz-Rokah

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

The pathogenesis of histiocytic neoplasms is driven by mutations activating the MAPK/ERK pathway, but little is known about the transcriptional and post-transcriptional alterations involved in these neoplasms. We analyzed microRNA (miRNA) expression in plasma samples and tissue biopsies of Erdheim–Chester disease (ECD) and Langerhans cell histiocytosis (LCH) patients. In silico analysis revealed a potential role of miRNAs in regulating gene expression in these neoplasms as compared with healthy controls (HC). NanoString analysis revealed 101 differentially expressed plasma miRNAs in 16 ECD patients as compared with 11 HC, 95% of which were downregulated. MiRNAs-15a-5p,-15b-5p,-21-5p,-107,-221-3p,-320e,-630, and let-7 family miRNAs were further evaluated by qRT-PCR in an extended cohort of 32 ECD patients, seven LCH and 15 HC. Six miRNAs (let-7a, let-7c, miR-15a-5p, miR-15b-5p, miR-107 and miR-630) were highly expressed in LCH plasma and tissue samples as compared with ECD. Pathway enrichment analysis indicated the miRNA contribution to inflammatory and pro-survival signaling pathways. Moreover, the let-7 family members were downregulated in untreated ECD patients as compared with HC, while treatment with MAPK/ERK signaling inhibitors for 16 weeks resulted in their upregulation, which was in parallel with the radiologic response seen by PET-CT. The study highlights the potential contribution of miRNA to the inflammatory and neoplastic characteristics of ECD and LCH.

Original languageEnglish
Article number3240
Pages (from-to)1-20
Number of pages20
JournalCancers
Volume12
Issue number11
DOIs
StatePublished - 1 Nov 2020
Externally publishedYes

Keywords

  • Erdheim–Chester disease
  • Histiocytosis
  • MAPK/ERK pathway
  • MicroRNA

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