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Loss of NOTCH2 Creates a TRIM28-Dependent Vulnerability in Small Cell Lung Cancer [human_bulk_RNA_seq]

ABSTRACT: Loss of NOTCH2 Creates a TRIM28-Dependent Vulnerability in Small Cell Lung Cancer [human_bulk_RNA_seq]

PROVIDER: PRJNA1263606 | ENA |

REPOSITORIES: ENA

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Loss of NOTCH2 Creates a TRIM28-Dependent Vulnerability in Small Cell Lung Cancer [human_bulk_RNA_seq]

Project description:Small cell lung cancer (SCLC) is a highly aggressive malignancy that lacks effective targeted therapies, in part due to frequent loss-of-function mutations in tumor suppressors and the absence of recurrent oncogenic drivers. Approximately 15% of SCLCs harbor inactivating mutations in NOTCH1 or NOTCH2, and most neuroendocrine-high SCLCs exhibit low NOTCH activity. Using CRISPR/Cas9 screening in primary cell lines derived from NOTCH1/2-isogenic SCLC genetically engineered mouse models, we identified TRIM28 as a synthetic lethal dependency in NOTCH2-inactivated SCLCs. Loss of TRIM28 in this context robustly induced expression of endogenous retroviruses, activated viral sensing pathways, and triggered a type I interferon response. Mechanistically, NOTCH2 inactivation increased reliance on TRIM28-mediated ERV silencing, creating a hyper-dependence on TRIM28 via the STING–MAVS–TBK1 axis. Notably, TRIM28 was essential for tumor growth only in the setting of NOTCH2 loss. These findings identify TRIM28 as a potential therapeutic target in NOTCH2-deficient or low-NOTCH2-expressing SCLC.

2025-07-10 | GSE297360 | GEO

Loss of NOTCH2 Creates a TRIM28-Dependent Vulnerability in Small Cell Lung Cancer [bulk_murine_RNA_seq]

2025-07-10 | GSE297361 | GEO

Loss of NOTCH2 Creates a TRIM28-Dependent Vulnerability in Small Cell Lung Cancer [ChIP-seq]

2025-07-10 | GSE297358 | GEO

Loss of NOTCH2 Creates a TRIM28-Dependent Vulnerability in Small Cell Lung Cancer [bulk_murine_RNA_seq]

Project description:Loss of NOTCH2 Creates a TRIM28-Dependent Vulnerability in Small Cell Lung Cancer [bulk_murine_RNA_seq]

| PRJNA1263603 | ENA

Loss of NOTCH2 Creates a TRIM28-Dependent Vulnerability in Small Cell Lung Cancer [ChIP-seq]

Project description:Loss of NOTCH2 Creates a TRIM28-Dependent Vulnerability in Small Cell Lung Cancer [ChIP-seq]

| PRJNA1263597 | ENA

Transcriptional impact of conditional loss of Notch2 from adult NSCs

Project description:Adult NSCs maintenance depends on intakt Notch signaling. The role of Notch2 has only been marginally studied in adult neurogenesis. To adress the role of the Notch2 paralogue we conditionally deleted Notch2 from the adult SVZ and analysed the Notch2-deficient cells at distinct time points.

2018-01-23 | GSE99916 | GEO

TRIM28 silences endogenous retroviruses in neural progenitor cells

Project description:Here we show that in neural progenitor cells (NPCs) TRIM28 silences transcription of two groups of endogenous retroviruses (ERVs): IAP1 and MMERVK10C. Derepression of ERVs in Trim28-deficient NPCs was associated with a loss of H3K9me3 and resulted in transcriptional upregulation and reverse transcription. These findings demonstrate a unique dynamic transcriptional regulation of ERVs in NPCs. Analysis of upregulation of ERVs in Trim28-deficient NPCs

2015-01-07 | E-GEOD-45930 | biostudies-arrayexpress

NOTCH2 mutants

Project description:NOTCH2 mutants

| PRJNA967022 | ENA

TRIM28 is essential for erythroblast differentiation in the mouse

Project description:We discovered that Trim28 genetic loss in the adult mouse leads to defective immature erythropoiesis in the bone marrow and consequently to anemia.We further found that TRIM28 controls erythropoiesis in a cell-autonomous manner by inducibly deleting Trim28 exclusively in hematopoietic cells. Finally, in the absence of TRIM28 we observed increased apoptosis as well as diminished expression of multiple erythroid transcription factors and heme biosynthetic enzymes in immature erythroid cells. Thus, TRIM28 is essential for the cell-autonomous development of immature erythroblasts in the bone marrow. To induce Cre recombinase from the Mx1Cre transgene, poly(I:C) was injected 5 times every other day. Mice were analyzed two weeks after completion of poly(I:C) administration. TRIM28 mutant mice generate two distinct types of immature erythroid cells; KOa, with 5-8% of the Trim28 gene remaining undeleted (still bearing 26% of residual mRNA), and KOb, with 1-4% of the gene remaining undeleted (and with 18% of mRNA remaining).

2013-10-04 | E-GEOD-49843 | biostudies-arrayexpress

(1) Effect of KLHL6 loss on the transcriptome in DLBCL upon NOTCH ligand stimulation. (2) Effect of KLHL6 and NOTCH2 loss on the transcriptome in DLBCL. (3) Effect of DLBCL-associated NOTCH2 mutants on the transcriptome in DLBCL.

Project description:(1) Assessment of the transcriptional changes regulated by KLHL6 upon NOTCH ligand stimulation. Bulk RNA-seq in KLHL6 WT or KO U2932 cells was performed upon incubation with stromal OP9 cells stably expressing NOTCH ligand DLL1. (2) Assessment of the transcriptional changes regulated by the KLHL6-NOTCH2 axis in a xenotransplant model of DLBCL. Bulk RNA-seq was performed in in KLHL6+/+NOTCH2+/+(WT), KLHL6-/-NOTCH2+/+(K6-KO), KLHL6+/+NOTCH2-/-(N2-KO), KLHL6-/-NOTCH2-/-(DKO) U2932 cells xenotranplanted in NSG mice trated with CHOP. (3) Assessment of the transcriptional changes regulated by the DLBCL-associated NOTCH2 mutants. Bulk RNA-seq was performed inU2932 cells stably expressing NOTCH2(WT), NOTCH2(S2156A), NOTCH2(R2400*) or NOTCH2(Q2140*).

2024-05-03 | GSE231624 | GEO

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