Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptional changes induced by miR-21 antagonism in T helper cells abrogates Th17 tumor promoting functions

ABSTRACT: Multiple myeloma (MM) is a hematologic malignancy tightly dependent on inflammatory bone marrow microenvironment. IL-17 producing CD4+ T cells (Th17) sustain MM cells growth and osteclast-dependent bone damage. In turn, Th17 generation and function rely on inflammatory stimuli. There is compelling evidence that miR-21 is involved in Th17 differentiation and effector functions. Here, we investigated the role of miR-21, which is an inflammation induced miRNA, in Th17-mediated MM tumor growth and bone disease. We found that inhibition of miR-21 in naive T cells (miR-21i-T cells) impaired differentiation towards Th17 in vitro. Analysis of miR-21-related molecular pathways in Th17 cells demonstrated upregulation of STAT-1/-5a-5b, downregulation of STAT-3 and redirection of Th17 to Th1/activated like cells as shown by a pair-to-pair RNAseq and proteome/phosphoproteome analysis. Inhibition of miR-21 impaired Th17 mediated MM cell proliferation and osteoclast activity in vitro. We recapitulated and validated these findings in NOD/SCID gNULL mice, injected intratibially with miR-21i-T cells and MM cells. Our findings disclose the critical involvement of miR-21 in pathogenic Th17 development and activity and open the avenue to the design of miR-21-targeting strategies to counteract microenviromental dependence of MM growth and bone disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE153287 | GEO | 2020/06/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The gene expression profiles of human multiple myeloma cell lines transfected with miR-10a mimic

Project description:In multiple myeloma (MM), abnormal plasma cells interact with bone marrow (BM) stromal cells and vascular cells among others. Bone marrow stromal cells (BMSCs) interact with MM cells in the bone marrow (BM), and also create a permissive microenvironment for MM cell growth and survival. Recent evidence indicated that extracellular vesicles (EVs)-mediated MM cell-BMSC communication plays an important role in the MM microenvironment. In this study, we investigated the biological property of the EVs and EV-miRNAs derived from BMSCs, aiming to establish the emerging strategies to target MM microenvironment to prevent tumor growth and spread. We found that the MM-BMSC-EVs enhanced the cell proliferation of RPMI8226. The EV-miRNA expression was different between MM-BMSCs and Normal-BMSCs, and some miRNAs, including miR-10a, were significantly up-regulated in the MM-BMSC-EVs. We then visualized with an in vitro model the uptake of Cy3-labeled miR-10a into RPMI8226 via EVs. To identify the function of miR-10a in MM cells, miR-10a mimic was transfected into RPMI8226 cells.

2018-09-30 | GSE118282 | GEO

microRNA profiling of multiple myeloma bone marrow

Project description:Bone marrow microenvironment in MM contains a unique miR signature, which is partially present and detectable in the peripheral blood. A subset of miRs (let-7i, miR-106b, miR-15a, and miR16) shows aberrant expression in the precursor lesion of MGUS, while aberrant expression of other miRs (let-7a, miR-15a/b, miR-19b, miR-20a, miR-21, miR-223, and miR-361) is associated with cell proliferation and disease progression.

2016-07-01 | GSE49261 | GEO

Transcriptome profiling reveals anti-inflammatory activity of miR-29b in multiple myeloma associated dendritic cells

Project description:Dendritic cells (DCs) are among the major components of multiple myeloma (MM)-associated bone-marrow microenvironment and are involved in MM progression, growth and chemo-resistance. We observed that after 24h co-culture with different MM cell lines, DCs downregulate miR-29b expression. To gain insight on the effects of miR-29b, we performed a transcriptome analysis of DCs after transient transfection of a negative control or miR-29b mimics and 24h co-culture with U266 cell line.

2018-10-10 | GSE104831 | GEO

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

microRNA profiling of multiple myeloma bone marrow

2016-07-01 | E-GEOD-49261 | biostudies-arrayexpress

microRNA-21 deletion impairs regulatory T cell function

Project description:Background: It has been found that miR-21 is increased in colonic tissues and decreased in peripheral blood regulatory T cells (Tregs) of patients with ulcerative colitis (UC). We aimed to investigate the influence of miR-21 on Tregs function in intestinal inflammation. Methods: Various CD4+ T cell populations were flow-cytometry sorted from miR-21-/- mice and littermates (WT) utilization in T-cell transfer colitis model and suppression of T cell activation and proliferation by Tregs. Gene expression was microarray-profiled and validated by qPCR, ELISA and immunofluorescence. miR-21 mimic and inhibitor studies and a 3’-untranslated region of SOCS5 luciferase report assay were used to validate the effect of miR-21. Results: As compared to their littermates, miR-21-/- mice have less Tregs in lymph nodes. miR-21-/- Tregs produced higher amount of SOCS5 and IFNγ, and lower amount of Jak3, Stat3, Stat5a, Foxp3, TGFβ1 and IL10. miR-21-/- Tregs reduced suppressive function in vitro and in vivo. Functional assays indicated that miR-21 could directly suppress SOCS5 expression. Conclusions: Expression and function of miR-21 are cell-type- and context- dependent. miR-21 deficiency result in impaired SOCS-JAK-STAT pathway activity in Tregs. miR-21 play a positive role in Tregs differentiation and suppressive function.

2017-09-29 | GSE104363 | GEO

The gene expression profiles of human bone marrow stromal cells derived from multiple myeloma patients

Project description:Bone marrow stromal cells (BMSCs) and their exosomes are a promising area of cancer therapy. Multiple myeloma (MM) is refractory hematologic malignancy. Bone marrow stromal cells (BMSCs) interact with MM cells in the bone marrow (BM), and also create a permissive microenvironment for MM cell growth and survival. Recent evidence indicated that exosome-mediated MM cell-BMSC communication plays an important role in the MM microenvironment. In this study, we investigated the biological property of the exosomes and exosomal miRNAs derived from BMSCs, aiming to establish the emerging strategies to target MM microenvironment to prevent tumor growth and spread.

2018-07-14 | GSE108915 | GEO

Expression profiling in exosomal miRNAs of human bone marrow stromal cells derived from multiple myeloma patients

2018-06-08 | GSE110271 | GEO

Expression profiling in cellular miRNAs of human bone marrow stromal cells derived from multiple myeloma patients

Project description:Bone marrow stromal cells (BMSCs) and their exosomes are a promising area of cancer therapy. Multiple myeloma (MM) is a refractory hematologic malignancy. Bone marrow stromal cells (BMSCs) interact with MM cells in the bone marrow (BM), and also create a permissive microenvironment for MM cell growth and survival. Recent evidence indicated that exosome-mediated MM cell-BMSC communication plays an important role in the MM microenvironment. In this study, we investigated the biological property of the exosomes and exosomal miRNAs derived from BMSCs, aiming to establish the emerging strategies to target MM microenvironment to prevent tumor growth and spread.

2018-06-08 | GSE110238 | GEO

Homo sapiens

Project description:HDMTX-21 pair

| PRJNA84609 | ENA