Genomics

Dataset Information

2

Lamin B1 loss promotes lung cancer development and metastasis by epigenetic derepression of RET [RNA-Seq]


ABSTRACT: Although abnormal nuclear structure is an important criterion for cancer diagnostics, remarkably little is known about its relationship to tumor development. Here we report that loss of lamin B1, a determinant of nuclear architecture, plays a key role in lung cancer. We found that lamin B1 levels were reduced in lung cancer patients. Lamin B1 silencing in lung epithelial cells promoted epithelial-mesenchymal transition, cell migration, tumor growth and metastasis. Mechanistically, we show that lamin B1 recruits the polycomb repressive complex 2 (PRC2) to alter the H3K27me3 landscape and repress genes involved in cell migration and signaling. In particular, epigenetic derepression of the RET proto-oncogene by loss of PRC2 recruitment, and activation of the RET/p38 signaling axis, play a crucial role in mediating the malignant phenotype upon lamin B1 disruption. Importantly, loss of a single lamin B1 allele induced spontaneous lung tumor formation and RET activation. Thus, lamin B1 acts as a tumor suppressor in lung cancer, linking aberrant nuclear structure and epigenetic patterning with malignancy. Overall design: RNA-seq analysis of control (n=2; Lmnb1_ctrl_MLE12_RNA_seq_rep1 and Lmnb1_ctrl_MLE12_RNA_seq_rep2) and lamin B1 knockdown (n=2; Lmnb1_KD_MLE12_RNA_seq_rep1 and Lmnb1_KD_MLE12_RNA_seq_rep2) MLE12 cells.

INSTRUMENT(S): Ion Torrent Proton (Mus musculus)

ORGANISM(S): Mus musculus  

SUBMITTER: Gergana Dobreva  

PROVIDER: GSE94680 | GEO | 2019-04-15

REPOSITORIES: GEO

Dataset's files

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GSE94680_Lmnb1_MLE12_RNA_seq_DEseq2_diffe_expression.xlsx Xlsx
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Publications


Although abnormal nuclear structure is an important criterion for cancer diagnostics, remarkably little is known about its relationship to tumor development. Here we report that loss of lamin B1, a determinant of nuclear architecture, plays a key role in lung cancer. We found that lamin B1 levels were reduced in lung cancer patients. Lamin B1 silencing in lung epithelial cells promoted epithelial-mesenchymal transition, cell migration, tumor growth, and metastasis. Mechanistically, we show that  ...[more]

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