Project description:Small Cell Lung Cancer (SCLC) is an aggressive neuroendocrine malignancy with a poor prognosis. Here, we focus on the neuroendocrine SCLC subtypes SCLC-A and SCLC-N, whose transcription addiction was driven by ASCL1 and NEUROD1 transcription factors which target E-box motifs to activate up to 40% of total genes, the promoters of which are maintained in a steadily open chromatin environment according to ATAC and H3K27Ac signatures. This leverage is used by the marine agent lurbinectedin, which preferentially targets the CpG islands located downstream of the transcription start site, thus arresting elongating RNAPII and promoting its degradation. This abrogates the expression of ASCL1 and NEUROD1 and of their dependent genes such as BCL2, INSM1, MYC and AURKA, which are responsible for relevant SCLC tumorigenic properties such as inhibition of apoptosis and cell survival, as well as for a part of its neuroendocrine features. In summary, we show how the transcription addiction of these cells becomes their Achilles' heel, and how this is effectively exploited by lurbinectedin as a novel and highly specific SCLC therapeutic endeavor.

2022-02-03 | GSE195663 | GEO

Human lung cancer cell lines DMS-273 (SCLC) and NCI-H1437 (NSCLC): scrambled vs. shRNA clones

Project description:Transcriptional profiling of two human lung cancer cell lines, DMS-273 (small cell lung cancer) and NCI-H1437 (non-small cell lung cancer), stably transfected either with innocuous scrambled shRNAs or SETDB1-specific.The objective was to identify global gene expression changes due to the depletion of the H3K9me3 methyltransferase SETDB1. 3 replicates for DMS-273 and 1 Control; 2 replicates for NCI-H1437 and 1 Control

2013-11-15 | E-GEOD-45175 | biostudies-arrayexpress

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