GEO series

The Lysine Demethylase Kdm4C is an Oncogenic Driver and Regulates ERK Activity in KRAS Mutant Pancreatic Ductal Adenocarcinoma [RNA-Seq]

GSE300083 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2025/12/16 Platform GPL24676Platform GPL18573

At a glance

RNA-seq (gene expression) · human · 12 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)
Samples: 12 samples: 3 × AsPC1, KDM4C WT, vs 3 × AsPC1, KDM4C KO1, vs 3 × AsPC1, shNT, Day 90, vs 3 × AsPC1, shKDM4C-1, Day 90,Groups 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: The Lysine Demethylase KDM4C Is an Oncogenic Driver and Regulates ERK Activity in KRAS-Mutant Pancreatic Ductal AdenocarcinomaCancer research communications · 2026

Summary (written by the submitters)

Deregulation of proteins involved in chromatin regulation is common in pancreatic ductal adenocarcinoma (PDAC). Lysine demethylase 4C (Kdm4C) is one of the chromatin-modifying proteins frequently overexpressed across multiple solid cancers and is linked to chromatin instability, increased cell proliferation, and enhanced stem cell-like behavior.

Read the full summary ↓

We observed upregulation of Kdm4C protein in a panel of human PDAC cell lines and patient samples compared to non-neoplastic controls. CRISPR/Cas9-mediated deletion of KDM4C in human and murine PDAC cells reduced proliferation, clonogenicity and increased survival of orthotopically implanted murine PDAC allografts. Transcriptomic and proteomics analyses revealed that loss of Kdm4C in both human and murine PDAC cell lines was associated with reduction of activated phospho-Erk, a pivotal effector downstream of mutant Ras. Using proximity labeling, we identified the histone deacetylase SIRT1 as a novel interacting protein with Kdm4C via the latter’s Tudor reader domain. SIRT1-mediated deacetylation leads to repression of downstream targets, including the dual specificity phosphatase DUSP2, which is known to inactivate Erk via dephosphorylation. In vitro propagation of KDM4C-null PDAC lines eventually led to adaptation and restitution of Erk signaling via compensatory upregulation of other KDM4 family members. To bypass this genetic compensation, we tested a preclinical pan-KDM4 inhibitor TACH107 and confirmed its efficacy in in vitro and in vivo PDAC models including those resistant to the covalent KRASG12D inhibitor MTRX1133. Our studies identify Kdm4C as an oncogenic molecule that sustains Erk signaling in KRAS-mutant PDAC and can be broadly targeted via small molecule inhibitors.

Published in

The Lysine Demethylase KDM4C Is an Oncogenic Driver and Regulates ERK Activity in KRAS-Mutant Pancreatic Ductal Adenocarcinoma

Shaheen MT, Dhebat S, Rajapakshe KI et al. · Cancer research communications 2026 · PMID 41490602 · doi:10.1158/2767-9764.CRC-25-0278

This dataset

Open GSE300083 in finder → Find more human RNA-seq datasets →

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 GSE300083_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 PRJNA1278994 and SRA study SRP592839. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41490602) ↗

Study design

3 × AsPC1, KDM4C WT, vs 3 × AsPC1, KDM4C KO1, vs 3 × AsPC1, shNT, Day 90, vs 3 × AsPC1, shKDM4C-1, Day 90,

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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

GSM9053558 AsPC1, KDM4C WT, rep1 AsPC1, KDM4C WT,
GSM9053559 AsPC1, KDM4C WT, rep2 AsPC1, KDM4C WT,
GSM9053560 AsPC1, KDM4C WT, rep3 AsPC1, KDM4C WT,
GSM9053561 AsPC1, KDM4C KO1, rep1 AsPC1, KDM4C KO1,
GSM9053562 AsPC1, KDM4C KO1, rep2 AsPC1, KDM4C KO1,
GSM9053563 AsPC1, KDM4C KO1, rep3 AsPC1, KDM4C KO1,
GSM9053564 AsPC1, shNT, Day 90, rep1 AsPC1, shNT, Day 90,
GSM9053565 AsPC1, shNT, Day 90, rep2 AsPC1, shNT, Day 90,
GSM9053566 AsPC1, shNT, Day 90, rep3 AsPC1, shNT, Day 90,
GSM9053567 AsPC1, shKDM4C-1, Day 90, rep1 AsPC1, shKDM4C-1, Day 9…
GSM9053568 AsPC1, shKDM4C-1, Day 90, rep2 AsPC1, shKDM4C-1, Day 9…
GSM9053569 AsPC1, shKDM4C-1, Day 90, rep3 AsPC1, shKDM4C-1, Day 9…

Datasets on a similar topic

GSE300200 The Lysine Demethylase Kdm4C is an Oncogenic Driver and Regulates ERK Activity in KRAS Mutant Pancreatic Ductal Adenocarcinoma 26 samples shares kdm4c, kras, erk, adenocarcinoma, demethylase, pancreatic, oncogenic, activity
GSE273073 A hPSC-Derived Progressive Pancreatic Ductal Adenocarcinoma Model Reveals Dual Pathways in ERK-Driven Cellular Plasticity 93 samples shares erk, adenocarcinoma, pancreatic
GSE272460 Transcriptome analysis of pancreatic progenitor organoids (POs) carrying PDAC related mutations, treated with ERK inhibitors and depleted of AP-1 factors 40 samples shares erk, pancreatic
GSE265906 Epigenetic and oncogenic inhibitors cooperatively drive differentiation and kill KRAS-mutant colorectal cancers [LOVO_BCat] 24 samples shares kras, oncogenic
GSE310675 CRISPR-Cas9 Screening Identifies Resistance Mechanisms to KRAS Inhibition in Pancreatic Cancer 12 samples shares kras, pancreatic
GSE205154 Bulk RNA-Seq gene expression data for 289 primary and metastatic pancreatic ductal adenocarcinoma (PDAC) tumor samples from FFPE blocks. 289 samples shares adenocarcinoma, pancreatic
GSE263733 Single-cell transcriptome analysis reveals subtype-specific clonal evolution and microenvironmental changes in liver metastasis of pancreatic adenocarcinoma and their clinical implications 218 samples shares adenocarcinoma, pancreatic
GSE310252 Transcriptome-based classification of resected pancreatic ductal adenocarcinoma enhances prognostic modelling accuracy of overall survival following adjuvant treatment 118 samples shares adenocarcinoma, pancreatic

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