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Series GSE262951 Query DataSets for GSE262951
Status Public on Apr 02, 2024
Title The TP53-activated E3 ligase RNF144B is a tumour suppressor that prevents genomic instability
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Background: TP53, the most frequently mutated gene in human cancers, orchestrates a complex transcriptional program crucial for cancer prevention. While certain TP53-dependent genes have been extensively studied, others, like the recently identified RNF144B, remained poorly understood. This E3 ubiquitin ligase has shown potent tumor suppressor activity in murine Eμ Myc-driven lymphoma, emphasizing its significance in the TP53 network. However, little is known about its targets and its role in cancer development, requiring further exploration. In this work, we investigate RNF144B's impact on tumor suppression beyond the hematopoietic compartment in human cancers. Methods: Employing TP53 wild-type cells, we generated models lacking RNF144B in both non-transformed and cancerous cells of human and mouse origin. By using proteomics, transcriptomics, and functional analysis, we assessed RNF144B's impact in cellular proliferation and transformation. Through In vitro and in vivo experiments, we explored proliferation, transformation potential, DNA repair, cell cycle control, mitotic progression, and treatment resistance. Findings were contrasted with clinical datasets and bioinformatics analysis. Results: Our research underscores RNF144B's pivotal role as a tumor suppressor, particularly in lung adenocarcinoma. In both human and mouse oncogene-expressing cells, RNF144B deficiency heightened cellular proliferation and transformation. Proteomic and transcriptomic analysis revealed RNF144B's novel function in mediating protein degradation associated with cell cycle progression, DNA damage response and genomic stability. RNF144B deficiency induced chromosomal instability, mitotic defects, and correlated with elevated aneuploidy and worse prognosis in human tumors. Furthermore, RNF144B-deficient lung adenocarcinoma cells exhibited resistance to cell cycle inhibitors that induce chromosomal instability. Conclusions: PRJNA1092607Supported by clinical data, our study suggests that RNF144B plays a pivotal role in maintaining genomic stability during tumor suppression.
Overall design MEFs were infected with the corresponding shRNAs in three independent biological replicas and sorted for GFP by flow cytometry using a BD Influx cell sorter (BD Biosciences).
cells were trypsinized and the pellet was snap frozen. RNA from 1 million cells was extracted using the Purelink RNA kit (10307963, Invitrogen) and submitted for analysis
Libraries were prepared using the TruSeq stranded mRNA Library Prep (20020594, Illumina) according to the manufacturer's protocol.
We were interested in the expression differences between RNF144B KD MEFs and those with shCTRL (shRENILLA)
Contributor(s) Abad E, Sandoz J, Romero G, Zadra I, Urgel-Solas J, Borredat P, Kourtis S, Ortet L, Martínez CM, Weghorn D, Sdelci S, Janic A
Citation(s) 38685100
BioProject PRJNA1092607
Submission date Apr 01, 2024
Last update date May 23, 2024
Contact name Gerard Romero
Organization name Universitat Pompeu Fabra
Department Dpt of Medicine and Life Sciences, Universitat Pompeu Fabra (MELIS/UPF)
Street address Doctor Aiguader, 88
City Barcelona
State/province Catalonia
ZIP/Postal code 08003
Country Spain
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (6)
GSM8182091 RNA-Seq of Mouse Embryonic Fibroblast: Transduced with control short-hairpin replicate 1
GSM8182092 RNA-Seq of Mouse Embryonic Fibroblast: Transduced with control short-hairpin replicate 2
GSM8182093 RNA-Seq of Mouse Embryonic Fibroblast: Transduced with control short-hairpin replicate 3

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Supplementary file Size Download File type/resource
GSE262951_raw_counts_matrix.txt.gz 403.9 Kb (ftp)(http) TXT
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Raw data are available in SRA

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