Regulation of Pkm2 by miR-122.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE29907 | GEO | 2014/06/08
SECONDARY ACCESSION(S): PRJNA140817
REPOSITORIES: GEO
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Project description:The study identified Pkm2 to be highly expressed in human embryonic stem cells and hepatocellular carcinoma cells, and targeted by a microRNA that is highly expressed in human primary hepatocytes. Gene expression patterns were compared from total RNA obtained from human embryonic stem cells, human primary hepatocytes, and hepG2 and hep3B.
2014-06-08 | E-GEOD-29907 | biostudies-arrayexpress
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: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.
2016-03-25 | GSE79535 | GEO
Project description:miR-122 is a highly-expressed liver microRNA that is activated perinatally and aids in regulating cholesterol metabolism and promoting terminal differentiation of hepatocytes. Disrupting expression of miR-122 can re-activate embryo-expressed adult-silenced genes, ultimately leading to the development of hepatocellular carcinoma (HCC). We interrogated the liver transcriptome at various time points after genomic excision of miR-122 to determine the cellular consequences leading to oncogenesis. Loss of miR-122 led to specific and progressive increases in expression of imprinted clusters of microRNAs and mRNA transcripts at the Igf2 and Dlk1-Dio3 loci that could be curbed by re-introduction of exogenous miR-122. mRNA targets of other abundant hepatic microRNAs became functionally repressed leading to widespread hepatic transcriptional de-regulation. Together, this reveals a transcriptomic framework for the hepatic response to loss of miR-122 and the outcome on other microRNAs and their cognate gene targets.
2018-10-07 | GSE111805 | 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
Project description:The liver-specific microRNA, miR-122, is an essential host factor for replication of hepatitis C virus (HCV), an important infectious cause of chronic liver disease and hepatocellular carcinoma. miR-122 stabilizes the positive-strand HCV RNA genome and promotes viral RNA synthesis by binding two closely spaced sites (S1 and S2) near the 5’ end of the genome in association with Ago2. Ago2 is essential for both host factor activities, but whether other host proteins are involved is unknown. Using a quantitative proteomics approach, we identified TNRC6A (GW182) and its paralogs (TNRC6B and TNRC6C), as functionally important components of the miR-122/Ago2 host factor complex binding HCV RNA. Depletion of any two TNRC6 proteins reduced HCV replication in Huh-7.5 cells,but did not reduce viral RNA stability or translational activity, but rather dampened miR-122 stimulation of viral RNA synthesis. However, TNRC6 depletion had no effect on replication of HCV in which S2 was mutated so that miR-122 binds only S1, whereas it significantly enhanced replication when S1 was mutated and only S2 bound by miR-122. Consistent with this, we found that TNRC6 proteins preferentially associate with the S1 site, and that the association of Ago2 with S2 is increased in TNRC6-depleted cells. Collectively, these data suggest a model in which TNRC6 proteins, which are known to interact with Ago2, preferentially direct the miR-122/Ago2 complex to S1 while restricting its association with S2, thereby fine tuning the spatial organization of miR-122/Ago2 complexes bound to the viral RNA.
2019-04-24 | PXD013054 | Pride
Project description:We profiled global gene expression for two separate lines of mouse embryonic fibroblasts and find that deletion of PKM2 and expression of PKM1 does not alter global gene expression profiles. We used microarrays to futher characterize the effects of PKM1 expression compared to PKM2 expression on global gene expression in mouse embryonic fibroblasts. Primary mouse embryonic fibroblast cells were used for RNA extraction and hybridization on Affymetrix microarrays. Intensity files were RMA normalized using Affymetrix expression console.
2015-05-01 | E-GEOD-60499 | biostudies-arrayexpress
Project description:Nuclear translocation of the key metabolic enzyme Pyruvate Kinase Isoform 2 (PKM2) is widely observed in cancer, but its contribution to gene regulation and pathogenesis remains unclear. Here we find that PKM2 specifically recognized folded RNA G-quadruplex (rG4) structures in vitro with high affinity. In human cells, nuclear PKM2 bound thousands of precursor mRNAs at potential rG4 sites and translocation of PKM2 to the nucleus resulted in increased expression of rG4-containing mRNAs.
2024-07-31 | GSE179817 | GEO
Project description:Flag-PKM2 was expressed in H1299 cells. Then the H1299 cells were treated with DMSO or 100nM MLN8237. Then, cell lysate was incubated with anti-Flag M2-agarose. Elutes were separated with 10% SDS-PAGE. The gel was stained with Coomassie Brilliant Blue. Visualized bands were excised and subjected to LC-MS/MS analysis. Then the phosphorylation sites of PKM2 were identified.
2023-03-11 | PXD036575 | Pride
Project description:Purpose: The goals of this study are to investigate the effect of PKM2 KO or TMEM33 overexpression on genes expression. Methods: Fresh PKM2 KO MCF7, PKM2 KO MDA-MB-231 and TMEM33 OE MDA-MB-231 cell pellets, and their respective parental cells, were used for RNA extraction. RNA sequencing libraries were prepared using the Illumina TruSeq RNA Library Prep Kit v2 following the manufacturer’s instructions. Each library was sequenced in single read mode, 1 x 50 bp, using the HiSeq4000 platform. Sequencing reads were aligned to human genome (hg38) by STAR (version 2.5.2b). Expression levels of genes annotated in GENCODE (version 24 for PKM2 KO and their parental cells; version 27 for TMEM33 OE and their control cells) were quantified by RSEM (version 1.3.0). Parameters of STAR and RSEM were set following ENCODE’s long RNA-seq processing pipeline. Differentially expressed genes were identified by DESeq2 (version 1.24.0) under the requirement of at least two-fold changes and an adjusted p-value < 0.05. Results: Differential gene expression analyses identified 269 and 504 significantly up-regulated and 204 and 289 significantly down-regulated genes in MDA-MB-231 and MCF7 PKM2 KO cells compared to their parental cells (>=2-fold, adjusted P value < 0.05); Gene set enrichment analysis (GSEA) showed that cholesterol homeostasis and fatty acid metabolism were among the top down-regulated pathways in MDA-MB-231 TMEM33 OE cells. Moreover, the differential gene expression profiles between PKM2 KO and TMEM33 OE cell lines were positively correlated. Notably, the mRNAs of genes related to cholesterol homeostasis were decreased in both PKM2 KO and TMEM33 OE cells. Conclusions: TMEM33 acts as a downstream effector of PKM2 that regulates activation of SREBPs and lipid metabolism.
2021-08-06 | GSE175956 | GEO