MYC is a major oncogenic driver of Multiple Myeloma (MM) and yet almost no therapeutic agents exist that target MYC in MM. Here we report that the let-7 biogenesis inhibitor LIN28B correlates with MYC expression in MM and is associated with adverse outcome. We also demonstrate that the LIN28B/let-7 axis modulates the expression of MYC, itself a let-7 target. Further, perturbation of the axis regulates the proliferation of MM cells in vivo in a xenograft tumor model. RNA sequencing and gene set enrichment analyses of CRISPR-engineered cells further suggest that the LIN28/let-7 axis regulates MYC and cell cycle pathways in MM. We provide proof-of-principle for therapeutic regulation of MYC through let-7 with an LNA-GapmeR containing a let-7b mimic in vivo, demonstrating that high levels of let-7 expression repress tumor growth by regulating MYC expression. These findings reveal a novel mechanism of therapeutic targeting of MYC through the LIN28B/let-7 axis in MM that may impact other MYC dependent cancers as well. Overall design: RNA sequencing of MOLP-8 cells transduced with lentiCRISPRv2 scrambled control or containing a sgRNA against LIN28B. Both control and LIN28B KO cells were sequenced in triplicate.
The LIN28B/let-7 axis is a novel therapeutic pathway in multiple myeloma.
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View SamplesDifferential expression of genes between Arabidopsis WRKY18/40 knock out and wild type plants, after 8 h post inoculation of powdery mildew pathogen.
Transcriptional reprogramming regulated by WRKY18 and WRKY40 facilitates powdery mildew infection of Arabidopsis.
Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Ars2 promotes proper replication-dependent histone mRNA 3' end formation.
Specimen part, Cell line, Treatment
View SamplesArs2 is a component of the nuclear cap-binding complex that is required for cellular proliferation and contributes to microRNA biogenesis. Arrays were performed to determine the repertoire of genes that change following knock-down of Ars2. Knock-down of DGCR8 was also performed to determine which changes in Ars2 knock-down cells resulted from defects in microRNA expression.
Ars2 promotes proper replication-dependent histone mRNA 3' end formation.
Specimen part, Cell line, Treatment
View SamplesCraniosynostosis (CS) is the congenital premature fusion of one or more cranial sutures and represents the more prevalent craniofacial malformation in humans, with an overall incidence of 1 out of 2000-3000 live births. Non-syndromic craniosynostoses (NSC) are believed to be multifactorial disorders, with a strong genetic component, due to possible genegene or geneenvironment interactions that remain to be clearly identified. In this study we delved into the molecular signaling acting in calvarial tissue and cells from patients affected by nonsynodromic midline craniosynostosis, using a comparative analysis between fused and unfused sutures of each affected individuals. Using comparative microarray tissue gene expression profiling we have identified a subset of genes involved in the structure and function of the primary cilium, including the Bardet-Biedl syndrome 9 (BBS9) gene, which was recently associated to sagittal synostosis in a GWAS study. We therefore characterized BBS9 expression and cilium-related signaling in cells isolated from patients calvarial bone.
BBS9 gene in nonsyndromic craniosynostosis: Role of the primary cilium in the aberrant ossification of the suture osteogenic niche.
Sex, Specimen part, Disease
View SamplesIn vitro experiment of stimulation of monocyte-derived dendritic cells with Saccaromyces cerevisiae in exponential growth phase. This experiment was performed to verify the comparability of microarray
Using pathway signatures as means of identifying similarities among microarray experiments.
No sample metadata fields
View SamplesIn this study, we used conditional knockout and gene expression approaches to understand global molecular and transciptional changes due to ablation of each integrin subunit.
Functional Redundancy between β1 and β3 Integrin in Activating the IR/Akt/mTORC1 Signaling Axis to Promote ErbB2-Driven Breast Cancer.
Specimen part
View SamplesWe used microarrays to detail the global program of gene expression underlying Parkinson's disease
A genomic pathway approach to a complex disease: axon guidance and Parkinson disease.
No sample metadata fields
View SamplesMM1S cells have been cultured under normoxic and hypoxic conditions, and gene expression profiling has been performed using the Affymetrix Human Genome U133 Plus 2.0 array.
Metabolic signature identifies novel targets for drug resistance in multiple myeloma.
Cell line
View Sampleswe evaluated the modulation of gene expression profile in PBMCs from patients with hypotalamic amenorrhea. We have employed whole genome microarray expression profiling as a discovery platform to identify genes differentially expressed upon metreleptin treatment at different time points, week 12, 24 and 36.
Selective capacity of metreleptin administration to reconstitute CD4+ T-cell number in females with acquired hypoleptinemia.
Treatment, Subject
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