TY - JOUR
T1 - The contribution of micrornas to the inflammatory and neoplastic characteristics of erdheim–chester disease
AU - Weissman, Ran
AU - Diamond, Eli L.
AU - Haroche, Julien
AU - Pillar, Nir
AU - Shapira, Guy
AU - Durham, Benjamin H.
AU - Buthorn, Justin
AU - Cohen, Fleur
AU - Ki, Michelle
AU - Stemer, Galia
AU - Ulaner, Gary A.
AU - Amoura, Zahir
AU - Emile, Jean François
AU - Mazor, Roei D.
AU - Shomron, Noam
AU - Abdel-Wahab, Omar I.
AU - Shpilberg, Ofer
AU - Hershkovitz-Rokah, Oshrat
N1 - Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/11/3
Y1 - 2020/11/3
N2 - 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.
AB - 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.
KW - Erdheim–Chester disease
KW - Histiocytosis
KW - MAPK/ERK pathway
KW - MicroRNA
UR - http://www.scopus.com/inward/record.url?scp=85095730946&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/cancers12113240
DO - https://doi.org/10.3390/cancers12113240
M3 - مقالة
C2 - 33153128
SN - 2072-6694
VL - 12
SP - 1
EP - 20
JO - Cancers
JF - Cancers
IS - 11
M1 - 3240
ER -
