Loss of EIF4G2 Mediates Aggressiveness in Distinct Endometrial Cancer Subpopulations with Adverse Outcomes in Patients
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE242717 | GEO | 2024/02/18
REPOSITORIES: GEO
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Project description:Loss of EIF4G2 Mediates Aggressiveness in Distinct Endometrial Cancer Subpopulations with Adverse Outcomes in Patients
| PRJNA1014413 | ENA
Project description:Aberrant translation from mRNAs to proteins plays a crucial role in the pathogenesis of various cancers. Here, we revealed that the key proteins involved in translation were up-regulated in two hepatocellular carcinoma (HCC) cohorts. Specifically, we identified the translation initiation factor EIF4G2 as a marker of poor prognosis, linked to unfavorable overall survival (OS) outcomes. Our in vitro and in vivo studies confirmed that EIF4G2 promotes the development and metastasis of HCC. As an essential translation initiation factor, EIF4G2 knockdown disrupts polyribosome stability and inhibits nascent protein synthesis in the Huh-7 and MHCC97H cell lines. By com-paring the proteome and transcriptome of Huh-7 cells, we further identified PLEKHA1 as an essential target of EIF4G2 with IRES-dependent translation. PLEKHA1 was able to rescue the inhibitory effects of EIF4G2 knockdown on cell migration and invasion in both Huh-7 and MHCC97H cells. This research provides novel insights into the critical role of EIF4G2-dependent translation in cancer, where PLEKHA1 promotes HCC progression.
2024-05-30 | PXD052695 |
Project description:We transfected siRNA-EIF4G2 and si-NC into Hep3B cells to explore the differentially expressed genes in cells and the affected intracellular signaling pathways after EIF4G2 knockdown
2023-12-14 | GSE163180 | GEO
Project description:Eukaryotic translation initiation factor (eIF) 4G2 is a long-known homologue of the canonical eIF4G1. However, unlike the latter, it does not bind eIF4E or PABP, thus it remains unclear what and when brings eIF4G2 onto a ribosome. Here we report results of ribosome profiling performed in NIH 3T3 eIF4G2 (DAP5) -/- cells.
2020-10-19 | GSE158136 | GEO
Project description:RNA-binding proteins control gene expression in cardiac fibroblasts during TGFb-driven fibrotic responses, including the eukaryotic translation initiation factor 4G2 (eIF4G2), which was known to facilitate alternative mRNA translation during cellular stresses. However, the precise role of eIF4G2 in cardiac fibroblast activation in response to fibrotic stress remains unclear. In this study, we found increased eIF4G2 protein levels in the hearts of heart failure patients and myocardial infarcted mice, as well as in TGFb-treated immortalized human and primary mouse cardiac fibroblasts. Depletion of eIF4G2 led to predominant translational downregulation of genes that are enriched in focal adhesion and extracellular matrix pathways. eIF4G2 knockdown reduced the proliferation, migration, and collagen secretion of TGFb-treated cardiac fibroblasts. Mechanistically, we found that the translation of IGFBP7 mRNA relies on eIF4G2, which is crucial for ECM production in response to pro-fibrotic stimuli. The interaction between eIF4G2 and a DEAD box RNA helicase DDX24 can regulate IGFBP7 protein expression in cardiac fibroblasts. Together, these findings suggest that the TGFb-eIF4G2-IGFBP7 axis establishes a novel translational regulatory circuit that governs cardiac fibroblast activation. Furthermore, conditional knockout of Eif4g2 in POSTN-positive myofibroblasts reduced cardiac fibrosis in the myocardial infarction mouse model, thus improving cardiac function. Our study provides insights into the molecular mechanism of eIF4G2-mediated translational regulation of crucial physiological mRNAs during cardiac fibroblast activation.
2024-07-31 | GSE239824 | GEO
Project description:RNA-binding proteins control gene expression in cardiac fibroblasts during TGFb-driven fibrotic responses, including the eukaryotic translation initiation factor 4G2 (eIF4G2), which was known to facilitate alternative mRNA translation during cellular stresses. However, the precise role of eIF4G2 in cardiac fibroblast activation in response to fibrotic stress remains unclear. In this study, we found increased eIF4G2 protein levels in the hearts of heart failure patients and myocardial infarcted mice, as well as in TGFb-treated immortalized human and primary mouse cardiac fibroblasts. Depletion of eIF4G2 led to predominant translational downregulation of genes that are enriched in focal adhesion and extracellular matrix pathways. eIF4G2 knockdown reduced the proliferation, migration, and collagen secretion of TGFb-treated cardiac fibroblasts. Mechanistically, we found that the translation of IGFBP7 mRNA relies on eIF4G2, which is crucial for ECM production in response to pro-fibrotic stimuli. The interaction between eIF4G2 and a DEAD box RNA helicase DDX24 can regulate IGFBP7 protein expression in cardiac fibroblasts. Together, these findings suggest that the TGFb-eIF4G2-IGFBP7 axis establishes a novel translational regulatory circuit that governs cardiac fibroblast activation. Furthermore, conditional knockout of Eif4g2 in POSTN-positive myofibroblasts reduced cardiac fibrosis in the myocardial infarction mouse model, thus improving cardiac function. Our study provides insights into the molecular mechanism of eIF4G2-mediated translational regulation of crucial physiological mRNAs during cardiac fibroblast activation.
2024-07-31 | GSE239823 | GEO
Project description:Learning and memory require activity-induced changes in mRNA translation within dendrites, but which mRNAs are involved and how they are regulated remain unclear. We combined proximity labeling with ribosome profiling and CLIP to monitor how depolarization impacts dendritic translation. For a functionally coherent set of transcripts highly enriched in mitochondrial genes, depolarization leads to enhanced uORF translation, eIF4G2 binding, and increased translation. Engineered reporters demonstrate that activity-dependent translational control is conferred by the 5’UTRs and that dendritic localization, eIF4G2 binding, and uORF translation are necessary and sufficient to mediate this regulation. Downstream, this drives activity-dependent changes in dendritic mitochondrial function. Our studies uncover an unanticipated mechanism by which activity-dependent uORF translational control by eIF4G2 enables the coupling of synaptic activity to local remodeling of dendrites.
2024-03-14 | GSE213082 | GEO
Project description:Learning and memory require activity-induced changes in dendritic translation, but which messenger RNAs (mRNAs) are involved and how they are regulated are unclear. Here, to monitor how depolarization impacts local dendritic biology, we employed a dendritically-targeted proximity labeling approach, followed by cross-linking immunoprecipitation (CLIP), ribosome profiling, and mass spectrometry. Depolarization of primary cortical neurons with KCl or the glutamate agonist DHPG causes rapid reprogramming of dendritic protein expression, where changes in dendritic mRNAs and proteins are weakly correlated. For a subset of pre-localized messages, depolarization increases translation of upstream open reading frames (uORFs) and their downstream coding sequences, enabling localized production of proteins involved in long term potentiation, cell signaling, and energy metabolism. This activity-dependent translation is accompanied by the phosphorylation and recruitment of the non-canonical translation initiation factor eIF4G2, and the translated uORFs are sufficient to confer depolarization-induced, eIF4G2-dependent translational control. These studies uncover an unanticipated mechanism by which activity-dependent uORF translational control by eIF4G2 couples activity to local dendritic remodeling.
2024-04-02 | PXD050222 | Pride
Project description:Different types of hair follicles can be found in the skin of mice. It is believed that the signals that control hair follicle differentiation arise from cells in a structure called the dermal papilla. Understanding the nature of those signals is of interest for the biology of the normal tissue. We have developed a technique for isolation of dermal cells by enzymatic digestion of intact skin. We have identified two subpopulations of cells that can be separated by FACS. The Sox2-positive CD133-positive cells are found exclusively in the dermal papillae of guard/awl/auchene hairs, while Sox2-negative, CD133-positive cells are found in the other hair follicle types. We compared these populations with unfractionated dermal cells. We isolated the following 3 populations of cells from the back skin of neonatal mice (P2) by Flow Cytometry: 1) GFP-CD133- Total dermal cells 2) GFP-CD133+ Dermal Papilla cells 3) GFP+CD133+ Dermal Papilla cells The yield is approximately 50,000 cells of each population.
2009-06-26 | E-GEOD-16801 | biostudies-arrayexpress
Project description:Osteosarcoma (OS) is an essential threatening tumor of bone in young adults. OS stem cells (OSCs) act a significant role in the occurrence, metastasis, drug resistance and recurrence of OS. CD133 is an integral membrane glycoprotein, which has been identified as an OSCs marker. However, the mechanisms of metastasis, chemoresistance and progression in CD133(+) OSCs need to be further explored. We aim to detect the lncRNA and mRNA profiles in CD133(+) cells compared with CD133(-) cells from the Saos-2 cell line in the present study.
2024-06-01 | GSE207333 | GEO