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Small cell lung cancer responds to inhibition of Jumonji enzyme in vitro and in vivo

GSE208446 Homo sapiens (human) RNA-seq (gene expression) 90 samples Submitted 2024/10/10 Platform GPL24676Platform GPL16791
At a glance

RNA-seq (gene expression) · human · 90 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Topic
Small cell lung cancerThis series is part of our curated briefing on it.
Samples
90 samples: 24 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Jumonji histone demethylases are therapeutic targets in small cell lung cancerOncogene · 2024
Summary (written by the submitters)
Small-cell lung cancer (SCLC) arises from neuroendocrine cells within the lung. Along with deletion or loss of function Rb and TP53 mutations, which occur in almost all cases, subsets of SCLC are driven by specific transcription factors including ASCL1, NEUROD1, POU2F3, or YAP1. Various MYC family members provide further inter-tumor heterogeneity.
Read the full summary ↓
Despite this heterogeneity in SCLC, current treatment for SCLC is subtype agnostic. Although most patients are initially responsive to first line etoposide and platin chemotherapy they soon develop resistance with no effective second line therapy. A recent large NCI screen showed that over 60 SCLC cell line models responded to 500+ investigational drugs in a manner highly correlated with etoposide responses, suggesting none of these drugs would provide benefit for SCLC therapy beyond current chemotherapy. By analyzing publicly available data of shRNA and CRISPR screens in addition to our own RNA-seq expression data we identified KDM4A as a potential candidate to target in SCLC. To underscore the potential of KDM4A as an anti-SCLC target, we tested chemotherapy drug and three JmjC KDM inhibitors across a panel of SCLC cell lines representing all the SCLC transcription factor subtypes and found that SCLC responses to JmjC KDM inhibitors do not correlate to their responses to chemotherapy. Furthermore, we found upon treatment with pan-JmjC KDM inhibitor, JIB-04, many genes in the ER stress signaling pathways are upregulated in SCLC lines, suggesting this is the mechanistic path leading to SCLC slower growth or death. Additionally, analysis found that JIB-04 resistant cells activate pro-survival pathways such as mTOR to perhaps overcome the effects of JIB-04 treatment. Furthermore, the loss of KDM4A in SCLC cell line led to slower proliferation and activity in the ER stress signaling pathway.
Published in
Jumonji histone demethylases are therapeutic targets in small cell lung cancer
Nguyen A, Nuñez CG, Tran TA et al. · Oncogene 2024 · PMID 39154123 · doi:10.1038/s41388-024-03125-x
This dataset
Open GSE208446 in finder → Find more human RNA-seq datasets → Small cell lung cancer landscape →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE208446_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA859939 and SRA study SRP386978. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39154123) ↗
Study design
24 conditions, mostly in triplicate
H446-DMSO ×9 H446-JIB-04 ×6 H446-CLX-DMSO ×6 H2171-DMSO ×3 H2171-JIB-04 ×3 HCC4001-DMSO ×3 HCC4001-JIB-04 ×3 H524-DMSO ×3 +28 more

Supports a between-group comparison across 78 samples.

How we read this: 24 replicated groups read from 90 sample titles; they account for 78 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

+ 50 more — browse all 90 samples with per-sample file links →

More Small cell lung cancer datasets

Search all human RNA-seq datasets in GEO →

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.