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RNA-seq profiles of Tp53, Prkar1a and Axin1 edited basal organoids from a mouse model of breast cancer

ABSTRACT: This study demonstrates the applicability of an in vivo CRISPR/Cas9 genome-wide screen in the BALB/c-Trp53+/– mouse model of breast cancer to identify novel tumor suppressor genes involved in mammary tumorigenesis. Preneoplastic mammary organoids were established from using sorted basal cells isolated from BALB/c-Trp53+/– mice. CRISPR/Cas9 screening was used to target Trp53, Axin1 and Prkar1a. To explore the potential molecular basis of the morphological differences, RNA-seq analysis was used to compare the Axin1/Trp53 and Prkar1a/Trp53-edited organoids and to organoids targeted by Trp53-only guides.

ORGANISM(S): Mus musculus

PROVIDER: GSE184070 | GEO | 2021/12/21

REPOSITORIES: GEO

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Expression alterations induced by restoration of AXIN1 expression in SNU449 hepatocellular carcinoma cells

Project description:Aberrant activation of Wnt/β-catenin signaling is observed in numerous cancers. In hepatocellular carcinoma activating mutations in CTNNB1 (20-25%) or loss of function mutations in AXIN1 (10%), AXIN2 (2%) and APC (1-2%) are observed. All these mutations lead to aberrant stabilization of β-catenin, which constitutively activates downstream Wnt/β-catenin target genes and triggers a genetic program resulting in tumor formation. However, in relation to AXIN1 mutations some reports have challenged whether these indeed result in tumor growth by enhancing β-catenin signaling (e.g. PMID: 16964294, 29525529). Several alternative pathways have also been linked to AXIN1 (ENSG00000103126), such as TGFβ, SAPK/JNK, p53, YAP/TAZ and c-myc. To identify which one of these or other unknown signaling routes are linked to AXIN1, using CRISPR-Cas9 genome editing, we have successfully repaired the homozygous p.R712* AXIN1 mutation present in the SNU449 hepatocellular carcinoma cell line. Next, using RNA sequencing the RNA expression patterns of 3 independent repaired clones were compared with 3 clones retaining the AXIN1 mutation. Surprisingly, only 5 genes were significantly altered in the repaired clones, among which AXIN2, a well-established β-catenin target gene. Thus, this analysis leads to the surprising observation that a commonly observed mutation in a hepatocellular tumor suppressor gene, is associated with minimal alterations in gene expression, at least in the SNU449 cell line.

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RNA-seq profiles of Tp53, Prkar1a and Axin1 edited basal organoids from a mouse model of breast cancer

Project description:RNA-seq profiles of Tp53, Prkar1a and Axin1 edited basal organoids from a mouse model of breast cancer

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Breast Cancer Suppressor Role of RUNX1: Estrogen-dependent Regulation of AXIN1 and b-catenin

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Prkar1a haploinsufficiency leads to an overall increase in tumors caused by other genetic defects or chemical induction

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2014-08-29 | E-GEOD-57650 | biostudies-arrayexpress

Expression data from mouse hepatocellular carcinomas developed in Axin1 hepatocyte deleted mice

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2016-02-22 | GSE65313 | GEO

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2015-01-18 | E-GEOD-57965 | biostudies-arrayexpress

Mus musculus strain:C57BL/6

Project description:CRISPR/Cas9 mutation of Vhl, Pten, Trp53

| PRJNA272478 | ENA