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A MIR17HG-derived Long Noncoding RNA Provides an Essential Chromatin Scaffold for Protein Interaction and Myeloma Growth

ABSTRACT: A MIR17HG-derived Long Noncoding RNA Provides an Essential Chromatin Scaffold for Protein Interaction and Myeloma Growth

PROVIDER: PRJNA860192 | ENA |

REPOSITORIES: ENA

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A MIR17HG-derived Long Noncoding RNA Provides an Essential Chromatin Scaffold for Protein Interaction and Myeloma Growth [array]

Project description:Long noncoding RNAs (lncRNA) can drive tumorigenesis and are susceptible to therapeutic intervention. Here, we used a large-scale CRISPR interference viability screen to interrogate cell growth dependency to lncRNA genes in multiple myeloma (MM), and identified a prominent role for the miR-17-92 cluster host gene (MIR17HG). We show that a MIR17HG-derived lncRNA, named lnc-17-92, is the main mediator of cell growth dependency acting in a microRNA- and DROSHA- independent manner. Lnc-17-92 provides a chromatin scaffold for the functional interaction between c-MYC and WDR82, thus promoting the expression of ACC1, the rate-limiting enzyme of de novo lipogenesis. Targeting MIR17HG pre-RNA with clinically applicable antisense molecules disrupts the transcriptional and functional activities of lnc-17-92, causing potent anti-tumor effects both in vitro and in vivo in three pre-clinical animal models, including a clinically relevant PDX-NSG mouse model. This study establishes a novel oncogenic function of MIR17HG and provides potent inhibitors for translation to clinical trials.

2025-07-01 | GSE208598 | GEO

A MIR17HG-derived Long Noncoding RNA Provides an Essential Chromatin Scaffold for Protein Interaction and Myeloma Growth [RNA-Seq]

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A MIR17HG-derived Long Noncoding RNA Provides an Essential Chromatin Scaffold for Protein Interaction and Myeloma Growth [array]

Project description:A MIR17HG-derived Long Noncoding RNA Provides an Essential Chromatin Scaffold for Protein Interaction and Myeloma Growth [array]

| PRJNA860197 | ENA

A MIR17HG-derived Long Noncoding RNA Provides an Essential Chromatin Scaffold for Protein Interaction and Myeloma Growth [RNA-Seq]

Project description:A MIR17HG-derived Long Noncoding RNA Provides an Essential Chromatin Scaffold for Protein Interaction and Myeloma Growth [RNA-Seq]

| PRJNA860198 | ENA

A MIR17HG-derived long noncoding RNA provides an essential chromatin scaffold for protein interaction and myeloma growth.

Project description:Long noncoding RNAs (lncRNAs) can drive tumorigenesis and are susceptible to therapeutic intervention. Here, we used a large-scale CRISPR interference viability screen to interrogate cell-growth dependency to lncRNA genes in multiple myeloma (MM) and identified a prominent role for the miR-17-92 cluster host gene (MIR17HG). We show that an MIR17HG-derived lncRNA, named lnc-17-92, is the main mediator of cell-growth dependency acting in a microRNA- and DROSHA-independent manner. Lnc-17-92 provides a chromatin scaffold for the functional interaction between c-MYC and WDR82, thus promoting the expression of ACACA, which encodes the rate-limiting enzyme of de novo lipogenesis acetyl-coA carboxylase 1. Targeting MIR17HG pre-RNA with clinically applicable antisense molecules disrupts the transcriptional and functional activities of lnc-17-92, causing potent antitumor effects both in vitro and in vivo in 3 preclinical animal models, including a clinically relevant patient-derived xenograft NSG mouse model. This study establishes a novel oncogenic function of MIR17HG and provides potent inhibitors for translation to clinical trials.

| S-EPMC10082365 | biostudies-literature

A MIR17HG-derived Long Noncoding RNA Provides an Essential Chromatin Scaffold for Protein Interaction and Myeloma Growth

Project description:This SuperSeries is composed of the SubSeries listed below.

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