Effect of knocking down PIEZO1 in gastric cancer cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE228690 | GEO | 2023/12/08
REPOSITORIES: GEO
Similar Datasets
Project description:In gastric cancer (GC), PIEZO1 was suggested to promote cell migration by interacting with Trefoil factor family 1 (TFF1) and serve as a therapeutic target against invasion and metastasis. In addition, PIEZO1 demonstrates abundant expression in most GC cell lines and primary samples and highly-expressed PIEZO1 is associated with poor disease-specific survival. As Yoda1 is known to be an agonist of PIEZO1, we try to explore the PIEZO1 function in GC by Yoda1 treatment.
2023-12-08 | GSE228691 | GEO
Project description:HOX proteins play fundamental roles during ontogenesis by interacting with other non-HOX gene-encoded partners and performing transcriptional functions, while aberrant activation of HOX members drives tumorigenesis. In this study, gastric cancer (GC) expression microarray data indicates that HOXB9 is a prominent upregulated HOX member in GC samples and is significantly associated with clinical outcomes and advanced TNM stages. However, the functional role of HOXB9 in GC remains contradictory in previous reports, and the regulatory mechanisms are elusive. By in silico and experimental analyses, we found HOXB9 was upregulated by a vital cell cycle-related transcription factor E2F1. Depleting HOXB9 causes G1 phase cell cycle arrest by downregulating CDK6 and a subset of cell cycle-related genes. Meanwhile, HOXB9 contributes to cell division and maintains the cytoskeleton in GC cells. PBX2 is a potential transcription factor for CDK6. We verified that HOXB9 interacts with PBX2 to form a heterodimer and upregulates CDK6. Knocking down CDK6 can phenocopy the tumor-suppressive effects of HOXB9 depletion. Inhibiting HOXB9 can enhance the anti-tumor effect of CDK6 inhibitors on GC growth. In conclusion, we elucidate the oncogenic role of HOXB9 and reveal CDK6 as its potent downstream modulator in GC.
2023-01-31 | GSE223763 | GEO
Project description:The Hippo-YAP1 pathway is an evolutionally conserved signaling cascade that controls organ size and tissue regeneration. Its dysregulation has been well-studied to promote tumor initiation and progression, including gastric cancer (GC). Although the Hippo-YAP1 signaling pathway regulates the expression of thousands of target genes, how these target genes contribute to the oncogenic program driven by YAP1 remains unknown. Here we identified the vital role of FOXP4 in YAP1-driven gastric carcinogenesis by maintaining stemness and promoting peritoneal metastasis. Knocking down FOXP4 impairs GC spheroid formation and inhibits stemness marker expression, while its upregulation potentiates the cancer cells with more stemness. RNA-seq analysis revealed SOX12 as functional downstream of FOXP4 in the YAP1-induced carcinogenesis. Targeting FOXP4 by 42-(2-Tetrazolyl) rapamycin in GC cells enhanced the 5-FU efficacies. Our findings have unveiled FOXP4 as a novel stemness marker that promotes tumorigenesis by upregulating SOX12. Additionally, we have identified FOXP4 as a direct target for modulating YAP1 signaling in GC. Therefore, the YAP1-FOXP4-SOX12 axis presents a promising therapeutic target for GC.
2024-07-13 | GSE267854 | GEO
Project description:PIEZO1 is a mechanically-activated ion channel that contributes to flow sensing in vascular endothelium. Moreover, deletion of endothelial PIEZO1 was recently found to suppress activation of Notch1 target genes in hepatic microvascular endothelium. Here, because of the liver’s dominant role in lipid regulation, we set out to test the novel hypothesis that endothelial PIEZO1 regulates hepatic lipid homeostasis. We performed bulk RNA sequencing on PIEZO1-deleted mice exposed to chow and high fat diets. Our transcriptomics analysis reveal unexpected relevance to lipid and glucose homeostasis.
2024-06-29 | E-MTAB-9996 | biostudies-arrayexpress
Project description:Purpose: Knocking down NCOA4 disrupted Thyroid hormone receptor beta agonist,GC-1, mediated terminal human erythroblast differentiation. Therefore, we conducted RNA-seq to profile the transcriptome changes in NCOA4 knocked down human erythroblasts.. Methods: Human CD34+ cells were transduced by lentiviruses encoding shRNAs targeting either LacZ (control) or NCOA4 atday 1 of culture. At day 14, cells were switched to terminal differentiation medium. Results: Using an optimized data analysis workflow, we have identified an ensemble of genes whose expression are discrupted by NCOA4 knockdown. Conclusions: There is a significant correlation between the degree of GC-1-mediated gene activation and the degree of NCOA4 knockdown-mediated gene repression.
2017-09-06 | GSE102582 | GEO
Project description:The propeller-shaped blades of the PIEZO1 and PIEZO2 ion channels partition into the plasma membrane and respond to indentation or stretching of the lipid bilayer, thus converting mechanical forces into signals that can be interpreted by cells, in the form of calcium flux and changes in membrane potential. While PIEZO channels participate in diverse physiological processes, from sensing the shear stress of blood flow in the vasculature to detecting a light touch on the surface of the skin, the molecular details that enable these mechanosensors to tune their responses over a vast dynamic range of forces remain largely uncharacterized. To survey the molecular landscape surrounding PIEZO channels at the cell surface, we employed a mass spectrometry-based proteomic approach to capture and identify extracellularly exposed proteins in the vicinity of PIEZO1. This PIEZO1-proximal interactome was enriched in surface proteins localized to cell junctions and signaling hubs within the plasma membrane. Functional screening of these interaction candidates by calcium imaging and electrophysiology in an overexpression system identified the adhesion molecule CADM1/SynCAM that slows the inactivation kinetics of PIEZO1 with little effect on PIEZO2. Conversely, we found that CADM1 knockdown accelerates inactivation of endogenous PIEZO1 in Neuro-2a cells. Systematic deletion of CADM1 domains indicate that the transmembrane region is critical for the observed effects on PIEZO1, suggesting that modulation of inactivation is mediated by interactions in or near the lipid bilayer.
2024-10-30 | PXD054618 | Pride
Project description:Piezo1 is a mechanosensitive ion channel that has gained recognition for its role in regulating diverse physiological processes. However, the influence of Piezo1 in inflammatory disease, including infection and tumor-immunity, is not well-studied. We postulated that Piezo1 links physical forces to immune regulation in myeloid cells. We discovered signal transduction via Piezo1 in myeloid cells and established this channel as the primary sensor of mechanical stress in these cells. Global inhibition of Piezo1 was protective against both cancer and septic shock and resulted in a diminution in suppressive myeloid cells. Moreover, deletion of Piezo1 in myeloid cells protected against cancer and increased survival in poly-microbial sepsis. Mechanistically, we show that mechanical stimulation promotes Piezo1-dependent myeloid cell expansion by suppressing Rb. We further show Piezo1-mediated silencing of Rb is regulated via upregulation of HDAC2. Collectively, our work uncovers Piezo1 as a targetable immune checkpoint that drives immune-suppressive myelopoiesis in cancer and infectious disease.
2020-08-21 | GSE155340 | GEO
Project description:The expression level of mRNA after knocking-down lncRNA-MEG3 showed a great significance. We performed microarray and transcriptome profiling in C2C12 cells after transfection lncRNA-MEG3 48 hours later to detail the expression of mRNA after knocking-down lncRNA-MEG3.
2020-12-24 | GSE155070 | GEO
Project description:Mechanical force is a fundamental regulator of bone development and homeostasis. Mechanosensitive osteocytes are the most abundant bone cells that form interconnected dendrites to respond to mechanical stimuli and interact with the bone-forming osteoblasts and the bone-remodeling osteoclasts. However, the molecular mechanisms underlying osteocyte maturation and dendrite formation remain unclear. By generating a Piezo1 "knock-out" osteocyte cell line, we identified a key role of Piezo1-mediated mechanotransduction in osteocyte differentiation. QRT-PCR analysis revealed delayed osteocyte differentiation in the Piezo1 KO cells relative to WT cells. By performing bulk RNA sequencing of WT and Piezo1 KO OCY454 cells at early (D1), intermediate (D14), and late (D28) stages of differentiation allowed for the identification of key signaling pathways in driving normal osteocyte dfiferentiation, as well as those regulated by Piezo1 mechanotransduction.
2024-09-20 | GSE277264 | GEO
Project description:Bleomycin (BLM) induces lung injury, leading to inflammation and pulmonary fibrosis. Regulatory T cells (Tregs) maintain self-tolerance and control host immune responses. However, little is known about their involvement in the pathology of pulmonary fibrosis. Here we show that a unique Treg subset that expresses trefoil factor family 1(Tff1) emerges in the BLM-injured lung. These Tff1-expressing Tregs (Tff1-Tregs) were induced by IL-33. Moreover, although Tff1 ablation in Tregs had no impact, selective ablation of Tff1-Tregs using an intersectional genetic method promoted pro-inflammatory features of macrophages in the injured lung and exacerbated the fibrosis. Taken together, our study revealed the presence of a unique Treg subset expressing Tff1 in BLM-injured lungs and their critical role in the injured lung to ameliorate fibrosis.
2024-08-19 | GSE267864 | GEO