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

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

PROVIDER: PRJNA437669 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6822790_1.fastq.gz	Fastqsanger.gz
	SRR6822790_2.fastq.gz	Fastqsanger.gz
	SRR6822791_1.fastq.gz	Fastqsanger.gz
	SRR6822791_2.fastq.gz	Fastqsanger.gz
	SRR6822792_1.fastq.gz	Fastqsanger.gz

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

Project description: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 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.

2018-06-01 | GSE111651 | GEO

RNASeq of bone lining niche cell components from myeloma-bearing mice treated daily with small molecule LDN193189 (LDN) or vehicle control

Project description:We compare gene expression in FACS-sorted bone lining cell components (stromal progenitors, osteoprogenitors, endothelial cells) from LDN193189 vs. vehicle-treated myeloma-bearing mice, and in myeloma cells flushed from the central marrow vs. myeloma cells digested from the bone-lining niche. The myeloma model used is the murine 5TGM1 cell line injected into immunocompetent KaLwRij mice. LDN193189 is a type 1 BMP receptor inhibitor.

2019-08-14 | GSE135785 | GEO

Interaction with Myeloma Suppresses Ciliogenesis and osteogenesis of Bone Marrow Stromal Cells

Project description:Impaired bone marrow stromal cells (BMSCs) within the bone niche of multiple myeloma (MM) patients are implicated in the development of myeloma bone disease (MBD) and disease progression. However, the specific mechanisms are not yet fully understood.

2024-04-19 | GSE263960 | GEO

Bone marrow niche

Project description:Bone marrow niche

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RNASeq of bone lining niche cell components from healthy vs. myeloma-bearing mice

Project description:We compare gene expression in FACS-sorted bone-lining cell components: stromal progenitors, osteoprogenitors and endothelial cells, from myeloma-bearing vs. from healthy mice, and also between myeloma cells flushed from the central bone marrow vs. myeloma cells digested from the bone surface (myeloma-bearing mice only). The myeloma model used is the 5TGM1 murine myeloma cell line, injected into immunocompetent KaLwRij mice.

2019-08-14 | GSE135691 | GEO

Osteoclasts Control Re-activation of Dormant Myeloma Cells by Remodeling the Endosteal Niche

Project description:Multiple myeloma is largely incurable, despite development of therapies that target myeloma cell-intrinsic pathways. Disease relapse is thought to originate from dormant myeloma cells, localized in specialized niches, which resist therapy and re-populate the tumor. However, little is known about the niche, and how it exerts cell-extrinsic control over myeloma cell dormancy and re-activation. In this study we track individual myeloma cells by intravital imaging as they colonize the endosteal niche, enter a dormant state and subsequently become activated to form colonies. We demonstrate that dormancy is a reversible state which is switched ‘on’ by engagement with bone lining cells or osteoblasts, and switched ‘off’ by osteoclasts remodeling the endosteal niche. Dormant myeloma cells are resistant to chemotherapy targeting dividing cells. The demonstration that the endosteal niche is pivotal in controlling myeloma cell dormancy highlights the potential for targeting cell-extrinsic mechanisms to overcome cell-intrinsic drug resistance and prevent disease relapse.

2015-11-30 | GSE57695 | GEO

Transcription profiling of human multiple myeloma aspirates (n=414) before treatment

2008-06-13 | E-GEOD-4581 | biostudies-arrayexpress

Transcription profiling of human newly diagnised multiple myeloma patients prior to treatment

2008-06-13 | E-GEOD-4452 | biostudies-arrayexpress

Transcription profiling of human plasma cell samples from multiple myeloma patients

Project description:Samples in this series are pre-treatment bone marrow aspirates from multiple myeloma patients. Experiment Overall Design: Samples in this series are: Experiment Overall Design: 1. CD-138-selected plasma cells from bone marrow of patients with newly diagnosed multiple myeloma subsequently treated with high dose therapy and stem cell transplants termed Total Therapy 2 (pre-treatment TT2) Experiment Overall Design: 2. CD-138-selected plasma cells from bone marrow of patients with newly diagnosed multiple myeloma subsequently treated with Total Therapy 3 (pre treatment TT3). Experiment Overall Design: Overall Design: Experiment Overall Design: Gene expression signatures were used to: 1) develop unsupervised hierarchical cluster classes; 2) establish links with outcome following stem cell transplantation

2008-06-13 | E-GEOD-2658 | biostudies-arrayexpress

Transcription profiling of human plasma cell samples from multiple myeloma patients before treatment

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2008-04-07 | E-GEOD-4204 | biostudies-arrayexpress

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