Epigenetic silencing of miR-125b is required for normal B-cell development

Li, Guideng; So, Alex Yick-Lun; Sookram, Reeshelle; Wong, Stephanie; Wang, Jessica K.; Ouyang, Yan; He, Peng; Su, Yapeng; Casellas, Rafael; Baltimore, David

doi:10.1182/blood-2018-01-824540

Cited by 40 publications

(32 citation statements)

References 28 publications

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“…In addition to osteoclastogenesis 16,17 , PRDM1 is involved in plasma cell fate determination 40 , and forced expression of miR-125b decreases PRDM1 levels in the human lymphoma cell line PC-K8 via its binding activity to Prdm1 3′UTR 41 . Of identified targets of miR-125b, physiological silencing of miR-125b is required in mouse granulocytic differentiation 42 and B-cell development 43 in vitro via the targeting of Jund and S1pr1, respectively. The other established target of miR-125b, Lyn28, is involved in myeloid vs. B-cell fate determination in mouse hematopoietic stem cell cultures 44 .…”

Section: Discussionmentioning

confidence: 99%

The matrix vesicle cargo miR-125b accumulates in the bone matrix, inhibiting bone resorption in mice

et al. 2020

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Communication between osteoblasts and osteoclasts plays a key role in bone metabolism. We describe here an unexpected role for matrix vesicles (MVs), which bud from boneforming osteoblasts and have a well-established role in initiation of bone mineralization, in osteoclastogenesis. We show that the MV cargo miR-125b accumulates in the bone matrix, with increased accumulation in transgenic (Tg) mice overexpressing miR-125b in osteoblasts. Bone formation and osteoblasts in Tg mice are normal, but the number of bone-resorbing osteoclasts is reduced, leading to higher trabecular bone mass. miR-125b in the bone matrix targets and degrades Prdm1, a transcriptional repressor of anti-osteoclastogenic factors, in osteoclast precursors. Overexpressing miR-125b in osteoblasts abrogates bone loss in different mouse models. Our results show that the MV cargo miR-125b is a regulatory element of osteoblast-osteoclast communication, and that bone matrix provides extracellular storage of miR-125b that is functionally active in bone resorption.

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Section: Discussionmentioning

confidence: 99%

The matrix vesicle cargo miR-125b accumulates in the bone matrix, inhibiting bone resorption in mice

et al. 2020

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“…Overexpression of miR-125b also leads to defects in the development of pre-B cells, and miR-125b inhibits differentiation of primary B cells into plasma cells. 89 Macrophages can be polarized into two different types of macrophages (M1 and M2). The M1 type promotes the inflammatory response, while the M2 type inhibits the inflammatory response.…”

Section: Mir-125b Controls Drug Resistance In Cancermentioning

confidence: 99%

<p>The Emerging Roles of miR-125b in Cancers</p>

Wang¹,

Zeng²,

Jiang³

2020

CMAR

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MicroRNAs (miRNAs) are endogenous, noncoding, single-stranded RNA molecules of 22 nucleotides in length. MiRNAs have both tumor-suppressive properties and oncogenic properties that can control critical processes in tumors. Mature miR-125b originates from miR-125b-1 and miR-125b-2 and leads to the degradation of target mRNAs or the inhibition of translation through binding to the 3′ untranslated regions (3′-UTR) of target mRNAs. Importantly, miR-125b is involved in regulating NF-κB, p53, PI3K/Akt/mTOR, ErbB2, Wnt, and another signaling pathways, thereby controlling cell proliferation, differentiation, metabolism, apoptosis, drug resistance and tumor immunity. This review aims to summarize the recent literature on the role of miR-125b in the regulation of tumorigenesis and to explore its potential clinical application in the diagnosis, prognosis and clinical treatment of tumors.

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“…The transduced cells were selected using puromycin, starting at 3 days post-transduction. Genome editing in the respective locus was examined using a surveyor assay, which was performed according to the manufacturer's instructions (Integrated DNA Technologies) (Li et al, 2018).…”

Section: Crispr Engineering Of Cell Linesmentioning

confidence: 99%

Kinetic Inference Resolves Epigenetic Mechanism of Drug Resistance in Melanoma

et al. 2019

SSRN Journal

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We resolved a mechanism connecting tumor epigenetic plasticity with non-genetic adaptive resistance to therapy, with MAPK inhibition of BRAF-mutant melanomas providing the model. These cancer cells undergo multiple, reversible drug-induced cell-state transitions, ultimately yielding a drug-resistant mesenchymal-like phenotype. A kinetic series of transcriptome and epigenome data, collected over two months of drug treatment and release, revealed changing levels of thousands of genes and extensive chromatin remodeling. However, a 3-step computational algorithm greatly simplified the interpretation of these changes, and revealed that the whole adaptive process was controlled by a gene module activated within just three days of treatment, with RelA driving chromatin remodeling to establish an epigenetic program encoding long-term phenotype changes. These findings were confirmed across several patient-derived cell lines and in melanoma patients under MAPK inhibitor treatment. Co-targeting BRAF and histone-modifying enzymes arrests adaptive transitions towards drug tolerance in epigenetically plastic melanoma cells and may be exploited therapeutically.

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Epigenetic silencing of miR-125b is required for normal B-cell development

Abstract: Key Points miR-125b is epigenetically silenced in B cells. Physiological silencing of miR-125b is required for normal B-cell development.

Cited by 40 publications

References 28 publications

The matrix vesicle cargo miR-125b accumulates in the bone matrix, inhibiting bone resorption in mice

The matrix vesicle cargo miR-125b accumulates in the bone matrix, inhibiting bone resorption in mice

<p>The Emerging Roles of miR-125b in Cancers</p>

Kinetic Inference Resolves Epigenetic Mechanism of Drug Resistance in Melanoma

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