Inhibition of microRNA-138 enhances bone formation in multiple myeloma bone marrow niche.

Autor: Tsukamoto S; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Løvendorf MB; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.; Center for RNA Medicine, Department of Clinical Medicine, Aalborg University Campus Copenhagen, Copenhagen, Denmark., Park J; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Salem KZ; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Reagan MR; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.; Maine Medical Center Research Institute, Scarborough, ME, USA., Manier S; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Zavidij O; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Rahmat M; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Huynh D; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Takagi S; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Kawano Y; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Kokubun K; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Thrue CA; Center for RNA Medicine, Department of Clinical Medicine, Aalborg University Campus Copenhagen, Copenhagen, Denmark.; Department of Haematology, Aalborg University Hospital, Aalborg, Denmark., Nagano K; Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Harvard Medical School, Boston, MA, USA., Petri A; Center for RNA Medicine, Department of Clinical Medicine, Aalborg University Campus Copenhagen, Copenhagen, Denmark.; Department of Haematology, Aalborg University Hospital, Aalborg, Denmark., Roccaro AM; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.; ASST Spedali Civili di Brescia, Clinical Research Development and Phase I Unit, Brescia, BS, Italy., Capelletti M; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Baron R; Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Harvard Medical School, Boston, MA, USA., Kauppinen S; Center for RNA Medicine, Department of Clinical Medicine, Aalborg University Campus Copenhagen, Copenhagen, Denmark. ska@dcm.aau.dk.; Department of Haematology, Aalborg University Hospital, Aalborg, Denmark. ska@dcm.aau.dk., Ghobrial IM; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. irene_ghobrial@dfci.harvard.edu.
Jazyk: angličtina
Zdroj: Leukemia [Leukemia] 2018 Aug; Vol. 32 (8), pp. 1739-1750. Date of Electronic Publication: 2018 Jun 20.
DOI: 10.1038/s41375-018-0161-6
Abstrakt: Myeloma bone disease is a devastating complication of multiple myeloma (MM) and is caused by dysregulation of bone remodeling processes in the bone marrow microenvironment. Previous studies showed that microRNA-138 (miR-138) is a negative regulator of osteogenic differentiation of mesenchymal stromal cells (MSCs) and that inhibiting its function enhances bone formation in vitro. In this study, we explored the role of miR-138 in myeloma bone disease and evaluated the potential of systemically delivered locked nucleic acid (LNA)-modified anti-miR-138 oligonucleotides in suppressing myeloma bone disease. We showed that expression of miR-138 was significantly increased in MSCs from MM patients (MM-MSCs) and myeloma cells compared to those from healthy subjects. Furthermore, inhibition of miR-138 resulted in enhanced osteogenic differentiation of MM-MSCs in vitro and increased the number of endosteal osteoblastic lineage cells (OBCs) and bone formation rate in mouse models of myeloma bone disease. RNA sequencing of the OBCs identified TRPS1 and SULF2 as potential miR-138 targets that were de-repressed in anti-miR-138-treated mice. In summary, these data indicate that inhibition of miR-138 enhances bone formation in MM and that pharmacological inhibition of miR-138 could represent a new therapeutic strategy for treatment of myeloma bone disease.
Databáze: MEDLINE
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