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| Status |
Public on Jan 15, 2023 |
| Title |
A truncated and catalytically inactive isoform of KDM5B histone demethylase accumulates in breast cancer cells and regulates H3K4 tri-methylation and gene expression |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
KDM5B histone demethylase is overexpressed in many cancers and plays an ambivalent role in oncogenesis, depending on the specific context. This ambivalence could be explained by the expression of KDM5B protein isoforms with diverse functional roles, which could be present at different levels in various cancer cell lines. We show here that one of these isoforms, namely KDM5B-NTT, accumulates in breast cancer cell lines due to remarkable protein stability relative to the canonical PLU-1 isoform, which shows a much faster turnover. This isoform is the truncated and catalytically inactive product of an mRNA with a transcription start site downstream of the PLU-1 isoform, and the consequent usage of an alternative ATG for translation initiation. It also differs from the PLU-1 transcript in the inclusion of an additional exon (exon-6), previously attributed to other putative isoforms. Overexpression of this isoform in MCF7 cells leads to an increase in bulk H3K4 methylation and induces derepression of a gene cluster, including the tumor suppressor Cav1 and several genes involved in the interferon-alpha and -gamma response. We discuss the relevance of this finding considering the hypothesis that KDM5B may possess regulatory roles independent of its catalytic activity.
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| Overall design |
Comparative gene expression profiling analysis of RNA-seq data for MCF7 and MDA-MB-231 cells over-expressing the KDM5B-NTT vs control samples.
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| Contributor(s) |
Licursi V, Di Nisio E, Negri R |
| Citation(s) |
36697763 |
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| Submission date |
Nov 26, 2022 |
| Last update date |
Apr 17, 2023 |
| Contact name |
Valerio Licursi |
| E-mail(s) |
valerio.licursi@uniroma1.it
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| Organization name |
Institute of Molecular Biology and Pathology (IBPM), National Research Council (CNR)
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| Department |
c/o Dept. Biology and Biotechnologies "C. Darwin", Sapienza University of Rome
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| Street address |
via degli Apuli, 4
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| City |
Rome |
| ZIP/Postal code |
00185 |
| Country |
Italy |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (16)
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| GSM6757073 |
MCF7, KDM5B-NTT overexpression, rep2 |
| GSM6757074 |
MCF7, control, rep3 |
| GSM6757075 |
MCF7, KDM5B-NTT overexpression, rep3 |
| GSM6757076 |
MCF7, control, rep4 |
| GSM6757077 |
MCF7, KDM5B-NTT overexpression, rep4 |
| GSM6757078 |
MDA-MB-231, control, rep1 |
| GSM6757079 |
MDA-MB-231, KDM5B-NTT overexpression, rep1 |
| GSM6757080 |
MDA-MB-231, control, rep2 |
| GSM6757081 |
MDA-MB-231, KDM5B-NTT overexpression, rep2 |
| GSM6757082 |
MDA-MB-231, control, rep3 |
| GSM6757083 |
MDA-MB-231, KDM5B-NTT overexpression, rep3 |
| GSM6757084 |
MDA-MB-231, control, rep4 |
| GSM6757085 |
MDA-MB-231, KDM5B-NTT overexpression, rep4 |
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| Relations |
| BioProject |
PRJNA905687 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE218819_normalized_counts_allsamples.txt.gz |
2.8 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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