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Series GSE228966 Query DataSets for GSE228966
Status Public on Aug 08, 2023
Title Phosphorylated nuclear DICER1 promotes open chromatin state and gastric cell fate in lung adenocarcinomas [Nanostring]
Organism Mus musculus
Experiment type Expression profiling by array
Summary DICER1 canonically regulates micro(mi)RNA-mediated epithelial-to-mesenchymal transition (EMT) in lung adenocarcinomas (LUADs). We discovered that KRAS/ERK pathway phosphorylates DICER1 causing its nuclear translocation; phosphomimetic Dicer1 contributes to tumorigenesis in mice. Mechanisms through which phospho-DICER1 regulates tumor progression remain undefined. Here, we show that phospho-DICER1 is expressed in invasive human LUADs and promotes late-stage tumor progression in mice with oncogenic Kras, independent of miRNAs and EMT. Strikingly, in mice, we observed that the AT2 tumor cells with phospho-DICER1 express endodermal (gastric) genes and display an open chromatin state such that there are sub-populations of tumors cells with alveolar-endodermal or only endodermal identity. Importantly, we also observed expression of gastric genes in human LUADs with phospho-DICER1. Mechanistically, we identify a chromatin-DICER1 nuclear complex comprised of Mediator complex subunit 12, CBX1, MACROH2A.1 and transcriptional regulators. Together, we propose that phosphorylated-nuclear DICER1 leads to lineage reprogramming of AT2 tumor cells to mediate lung cancer progression.
Overall design For miRNA expression assay, lung tumors from KrasLA1/+;Dicer1S2D/+ mice (n=5) were compared to lung tumors from Kras LA1/+ mice (n=4). KrasLA1 mouse model have an oncogenic Kras G12D mutation. And KrasLA1/+;Dicer1S2D/+ have a heterozygous phosphomimetic Dicer1 in where serienes 1712 and 1836 were replaced to aspartic acid, in a heterozygous Kras LA1 oncogenic background. For this experiment, 30 to 37 weeks old mice from both genotypes were used. A total of 50mg of lung tumors per mouse was used and 577 miRNAs were analyzed using Nanostring nCounter mouse miRNA array..
Contributor(s) Reyes-Castro RA, Chen S, Seemann J, Lozano G, Arur S
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Submission date Apr 04, 2023
Last update date Aug 09, 2023
Contact name Raisa Reyes-Castro
Organization name UT Health MD Anderson Cancer Center
Department Genetics
Lab Swathi Arur
Street address 6767 Bertner Ave
City Houston
State/province Texas
ZIP/Postal code 77030
Country USA
Platforms (1)
GPL33314 nCounter Nanostring mouse miRNA (NS_M_MIR_V1.5)
Samples (9)
GSM7146668 Mouse Lung tumor_KrasLA1;DicerS2D_rep1
GSM7146670 Mouse Lung tumor_KrasLA1_rep1
GSM7146671 Mouse Lung tumor_KrasLA1;DicerS2D_rep2
This SubSeries is part of SuperSeries:
GSE228968 Phosphorylated nuclear DICER1 promotes open chromatin state and gastric cell fate in lung adenocarcinomas
BioProject PRJNA952253

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE228966_Nanostring_miRNA_normalized_data.csv.gz 18.0 Kb (ftp)(http) CSV
GSE228966_RAW.tar 60.0 Kb (http)(custom) TAR (of RCC)
Processed data included within Sample table
Processed data are available on Series record

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