NONO associates with PKM2 and directs histone H3 phosphorylation to promote tumor metastasis (CUT&Tag)
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ABSTRACT:
PROVIDER: PRJNA1106065 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28840753_1.fastq.gz | Fastqsanger.gz | |||
| SRR28840753_2.fastq.gz | Fastqsanger.gz | |||
| SRR28840754_1.fastq.gz | Fastqsanger.gz | |||
| SRR28840754_2.fastq.gz | Fastqsanger.gz | |||
| SRR28840755_1.fastq.gz | Fastqsanger.gz |
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Project description:Dysregulation of transcriptional programming and epigenome has been identified as fundamental driver of cancer. However, the molecular mechanisms in such processes remain poorly understood. Here, we report that NONO (non-POU domain-containing octamer-binding protein) directly interacts with nuclear PKM2, which is critical for the activation of the NONO-driven transcriptional programme in triple-negative breast cancer (TNBC). We further demonstrate that plasminogen activator inhibitor 1 (PAI1) is a downstream target of NONO/PKM2 complex in TNBC cells through transcriptome analysis. In addition, we show that PKM2-mediated phosphorylation of histone H3 at threonine 11 (H3T11ph) collaborates with acetylation of histone H3 at lysine 27 (H3K27ac), which is due, at least in part, to PKM2 transcriptional activation of TIP60 expression. Importantly, NONO, H3T11ph, and H3K27ac signals are co-enriched at the PAI1 gene loci, which directly boosts PAI transcription. Consistent with above results, we also confirm that the expression of NONO and PKM2 are positively correlated with PAI1 expression in TNBC tissues. Thus, our findings reveal nuclear PKM2 as a novel NONO cofactor required for its biological function and suggest that the NONO/PKM2-PAI1 axis is an attractive therapeutic target in TNBC.
2025-03-19 | GSE266177 | GEO
Project description:Dysregulation of transcriptional programming and epigenome has been identified as fundamental driver of cancer. However, the molecular mechanisms in such processes remain poorly understood. Here, we report that NONO (non-POU domain-containing octamer-binding protein) directly interacts with nuclear PKM2, which is critical for the activation of the NONO-driven transcriptional programme in triple-negative breast cancer (TNBC). We further demonstrate that plasminogen activator inhibitor 1 (PAI1) is a downstream target of NONO/PKM2 complex in TNBC cells through transcriptome analysis. In addition, we show that PKM2-mediated phosphorylation of histone H3 at threonine 11 (H3T11ph) collaborates with acetylation of histone H3 at lysine 27 (H3K27ac), which is due, at least in part, to PKM2 transcriptional activation of TIP60 expression. Importantly, NONO, H3T11ph, and H3K27ac signals are co-enriched at the PAI1 gene loci, which directly boosts PAI transcription. Consistent with above results, we also confirm that the expression of NONO and PKM2 are positively correlated with PAI1 expression in TNBC tissues. Thus, our findings reveal nuclear PKM2 as a novel NONO cofactor required for its biological function and suggest that the NONO/PKM2-PAI1 axis is an attractive therapeutic target in TNBC.
2025-03-19 | GSE266179 | GEO
Project description:NONO associates with PKM2 and directs histone H3 phosphorylation to promote tumor metastasis (RNA-Seq)
| PRJNA1106066 | ENA
Project description:Alternative splicing of the Pkm gene product generates the PKM1 and PKM2 isoforms of pyruvate kinase, and PKM2 expression is closely linked to embryogenesis, tissue regeneration, and cancer. To interrogate the functional requirement for PKM2 during development and tissue homeostasis, we generated germline PKM2 null mice (Pkm2-/-). Unexpectedly, despite being the primary isoform expressed in most wild-type adult tissues, we found that Pkm2-/- mice are viable and fertile. Thus, PKM2 is not required for embryonic or postnatal development. Loss of PKM2 leads to compensatory expression of PKM1 in the tissues that normally express PKM2. Strikingly, PKM2 loss leads to spontaneous development of hepatocellular carcinoma (HCC) with high penetrance that is accompanied by progressive changes in systemic metabolism characterized by altered systemic glucose homeostasis, inflammation, and hepatic steatosis. Therefore, in addition to its role in cancer metabolism, PKM2 plays a role in controlling systemic metabolic homeostasis and inflammation, thereby preventing HCC by a non-cell-autonomous mechanism. RNA was isolated from flash frozen ground whole liver tissue of 35 week old PKM2 KO and WT mice. Three independent mice from each condition were used as biological replicates.
2016-03-25 | E-GEOD-79535 | biostudies-arrayexpress
Project description:Identifying causes of sporadic intellectual disability remains a considerable medical challenge. Here, we demonstrate that null mutations in the NONO gene, a member of the Drosophila Behavior Human Splicing (DBHS) protein family, are a novel cause of X-linked syndromic intellectual disability. Comparing humans to Nono-deficient mice revealed related behavioral and craniofacial anomalies, as well as global transcriptional dysregulation. Nono-deficient mice also showed deregulation of a large number of synaptic transcripts, causing a disorganization of inhibitory synapses, with impaired postsynaptic scaffolding of gephyrin. Alteration of gephyrin clustering could be rescued by over-expression of Gabra2 in NONO-compromised neurons. These findings link NONO to intellectual disability and first highlight the key role of DBHS proteins in functional organization of GABAergic synapses.
2015-09-02 | E-MTAB-2895 | biostudies-arrayexpress
Project description:Identifying causes of sporadic intellectual disability remains a considerable medical challenge. Here, we demonstrate that null mutations in the NONO gene, a member of the Drosophila Behavior Human Splicing (DBHS) protein family, are a novel cause of X-linked syndromic intellectual disability. Comparing humans to Nono-deficient mice revealed related behavioral and craniofacial anomalies, as well as global transcriptional dysregulation. Nono-deficient mice also showed deregulation of a large number of synaptic transcripts, causing a disorganization of inhibitory synapses, with impaired postsynaptic scaffolding of gephyrin. Alteration of gephyrin clustering could be rescued by over-expression of Gabra2 in NONO-compromised neurons. These findings link NONO to intellectual disability and first highlight the key role of DBHS proteins in functional organization of GABAergic synapses.
2015-09-02 | E-MTAB-2894 | biostudies-arrayexpress
Project description:To investigate the RNA binding proterties of NONO and NONO-delta-ER in testis; we collected adult NONO and NONO-delta-ER mice testis We then performed eCLIP-seq respectively and convey subsequent bioinformatic analysis.
2024-08-08 | GSE263329 | GEO
Project description:siRNA knockdown of NONO mRNA followed by RNA-seq was carried out in the KELLY neuroblasotma cell line. In order to determine potential regulatory targets of NONO protein, we performed differential expression analysis. To identify the RNA targets of NONO in neuroblastoma, we carried out PAR-CLIP (Photoactivatable Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation) using an antibody recognising NONO protein.
2023-01-28 | GSE114376 | GEO
Project description:Pyruvate kinase M2 (PKM2) plays an important role in the consumption of glucose and the production of lactic acid, the striking feature of cancer metabolism. The association of PKM2 with osteosarcoma (OS) has been reported but its role in OS has not. To study this, we obtained PKM2-bound RNAs in HeLa cells. Peak calling analysis revealed that PKM2 binds to long noncoding RNAs (lncRNAs), which are associated with cancer pathogenesis and development. Validation of the PKM2-lncRNA interaction in the human OS cell line showed that lncRNA colon cancer associated transcript-1 (lncRNACCAT1) interacts with PKM2, which upregulates the phosphorylation of sterol regulatory element-binding protein 2. These factors promote the Warburg effect, lipogenesis, and OS cell growth. PKM2 seems to be a key regulator in OS by binding to lncCCAT1. This further extends the biological functions of PKM2 in tumorigenesis and makes it a novel potential therapeutic for OS.
2022-03-23 | GSE184327 | GEO
Project description:Purpose: In this study, we compared transcriptome profiling (RNA-seq) between normal mouse embryonic stem cell (E14) and Hexokinase2 (Hk2)/ Pyruvate Kinase M2 (Pkm2) overexpressed E14 cell. Result: Using an optimized data analysis workflow, we mapped over 4 billion sequence reads per sample to the mouse genome (build mm9) and identified 28698 transcripts in 5 samples. Conclusion: Our study represents the first detailed analysis of Hk2/ Pkm2 overexpressed E14 cell transcriptomes, generated by RNA-seq technology We compared transcriptome profiling (RNA-Seq) between normal mouse embryonic stem cell (E14) and E14 cells over-expressing Hexokinase2 (Hk2)/Pyruvate Kinase M2 (Pkm2)
2016-07-03 | E-GEOD-65246 | biostudies-arrayexpress