miR-15a targets the HSP90 co-chaperone Morgana in chronic myeloid leukemia

• Published in: Scientific reports 2024-07, Vol.14 (1), p.15089-11, Article 15089
• Main Authors: Poggio, Pietro, Rocca, Stefania, Fusella, Federica, Ferretti, Roberta, Ala, Ugo, D’Anna, Flora, Giugliano, Emilia, Panuzzo, Cristina, Fontana, Diletta, Palumbo, Valeria, Carrà, Giovanna, Taverna, Daniela, Gambacorti-Passerini, Carlo, Saglio, Giuseppe, Fava, Carmen, Piazza, Rocco, Morotti, Alessandro, Orso, Francesca, Brancaccio, Mara
• Format: Article
• Language: English
• Subjects: 631/337/384/331; 631/67/1990/283/1896; 631/80/470/1981; Animals; Apoptosis; Binding sites; Bone marrow; Bone Marrow - metabolism; Bone Marrow - pathology; Cancer; Chronic myeloid leukemia; Down-Regulation; Gene Expression Regulation, Leukemic; Genes; Hematology; HSP90 Heat-Shock Proteins - genetics; HSP90 Heat-Shock Proteins - metabolism; Hsp90 protein; Humanities and Social Sciences; Humans; Imatinib; Kinases; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Malignancy; Metastasis; Mice; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Molecular Chaperones - genetics; Molecular Chaperones - metabolism; multidisciplinary; Mutation; Myelodysplastic syndrome; Myeloid leukemia; Neutrophilia; Proteins; Science; Science (multidisciplinary); Stem cells; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-65404-7

Morgana is a ubiquitous HSP90 co-chaperone protein coded by the CHORDC1 gene. Morgana heterozygous mice develop with age a myeloid malignancy resembling human atypical myeloid leukemia (aCML), now renamed MDS/MPN with neutrophilia. Patients affected by this pathology exhibit low Morgana levels in the bone marrow (BM), suggesting that Morgana downregulation plays a causative role in the human malignancy. A decrease in Morgana expression levels is also evident in the BM of a subgroup of Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) patients showing resistance or an incomplete response to imatinib. Despite the relevance of these data, the mechanism through which Morgana expression is downregulated in patients’ bone marrow remains unclear. In this study, we investigated the possibility that Morgana expression is regulated by miRNAs and we demonstrated that Morgana is under the control of four miRNAs (miR-15a/b and miR-26a/b) and that miR-15a may account for Morgana downregulation in CML patients.