SUMOylation-Induced Membrane Localization of TRPV1 Suppresses Proliferation and Migration in Gastric Cancer Cells
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ABSTRACT:
PROVIDER: PRJNA1091614 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28454016_1.fastq.gz | Fastqsanger.gz | |||
| SRR28454016_2.fastq.gz | Fastqsanger.gz | |||
| SRR28454017_1.fastq.gz | Fastqsanger.gz | |||
| SRR28454017_2.fastq.gz | Fastqsanger.gz | |||
| SRR28454018_1.fastq.gz | Fastqsanger.gz |
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Project description:Gastric cancer (GC) remains a significant health challenge due to its high mortality rate and the limited efficacy of current targeted therapies. A critical barrier in developing more effective treatments is the lack of understanding of specific mechanisms driving GC progression. This study investigates the role of Transient Receptor Potential Vanilloid 1 (TRPV1), a non-selective cation channel known for its high Ca2+ permeability and tumor-suppressive properties in gastrointestinal cancers. Specifically, we explore the impact of SUMOylation—a dynamic and reversible post-translational modification—on TRPV1's function in GC. We demonstrate that SUMOylation of TRPV1 inhibits cell proliferation and migration in MGC-803 and AGS gastric cancer cells. By mutating amino acids near TRPV1's existing SUMO motif (slKpE), we created a bidirectional SUMO motif (EψKψE) that enhances TRPV1 SUMOylation, resulting in further suppression of GC cell proliferation and migration. In vivo studies support these findings, showing that TRPV1 SUMOylation prevents spontaneous tumorigenesis in a mouse gastric cancer model. Further investigation reveals that TRPV1 SUMOylation increases the protein's membrane expression by inhibiting its interaction with the adaptor-related protein complex 2 mu 1 subunit (AP2M1). This elevated membrane expression leads to increased intracellular Ca2+ influx, activating the AMP-activated protein kinase (AMPK) pathway, which in turn inhibits the proliferation and migration of GC cells. In conclusion, our study elucidates a novel mechanism wherein TRPV1 SUMOylation promotes its membrane expression and activates the TRPV1-Ca2+-AMPK signaling pathway, thereby inhibiting GC cell proliferation and migration. These findings enhance our understanding of the molecular dynamics in gastric cancer and could provide a new theoretical basis for clinical treatment strategies.
2024-10-15 | GSE262378 | GEO
Project description:To examine the functional significance of TRPV1 SUMOylation in vivo, we created a TRPV1K823R KI transgenic mouse line.We thus performed gene expression profiling analysis using data obtained from RNA-seq of the trigeminal ganglion of TRPV1K823R and control mouse models . Our analyses unveiled a role for TRPV1 SUMOylation in regulating gene networks related to the pain and itch pathway.
2022-06-14 | GSE203197 | GEO
Project description:TRPV1 SUMOylation suppresses itch by inhibiting TRPV1 interaction with H1 receptors
| PRJNA838996 | ENA
Project description:High migration and invasion ability of PGCCs and their daughter cells associated with the nuclear localization of S100A10 modified by SUMOylation
| PRJNA735527 | ENA
Project description:We developed an approach to rapidly eliminate the subgroup of sensory neurons expressing the heat-gated cation channel TRPV1 from dissociated rat sensory ganglia using agonist treatment followed by density centrifugation. To identify transcripts predominantly expressed in TRPV1-positive neurons, we compared the transcriptome of all cells within sensory ganglia versus all cells without TRPV1 expressing neurons using RNA-Seq.
2015-12-30 | E-MTAB-2789 | biostudies-arrayexpress
Project description:Purpose: S100A10 uesed to located in the cell membrane or cytoplasm. However nuclear-located S100A10 was observed in the polyploid tumor giant cells(PGCCs) with daughter cells induced by cobalt chloride(CoCl2). To study the function of nuclear-located S100A10, we performed ChIP-Seq. Methods:LoVo and Hct116 cells were incubated in T25 flasks in RPMI-1640 medium until they reached 80-90% confluence. The cells were treated with 450 μM CoCl2 (Sigma-Aldrich, St. Louis, MO, USA) for 48-72h based on their resistance to hypoxia. After the treatment with CoCl2 was repeated for 3-4 times, there were 20-30% of PGCCs and 70-80% of small-sized daughter cells that originated from PGCCs among the total cells.ChIP assays were performed according to the instructions of the Pierce Magnetic ChIP Kit (Thermo Fisher Scientific, #26157) For data analysis of ChIP DNA, sequencing and library preparation were performed using Novogene Technology Co., Ltd. (Tianjin, China). Raw data (raw reads) of FASTQ format were first processed through in-house PERL scripts, and then reference genome and gene model annotation files were downloaded directly from the genome website. For a specific ChIP-seq binding site, individual reads were mapped to the plus or minus strand and presented significant enrichment. After mapping the reads to the reference genome, the MACS2 version 2.1.0 (model-based analysis of ChIP-seq) peak finding algorithm was used to identify regions of specific IP enrichment over background. A p-value threshold of enrichment of 0.05 was used for all data sets. The interaction between transcription factor or chromatin histone modification and DNA was not random, but they showed some specific sequence preference. MEME 52 and DREME 53 were used to detect the sequence motif, which was used to detect long and short consensus sequences. The position of peak summit around the transcript start sites of genes can predict the interaction sites of proteins and genes. Genes associated with different peaks were identified, and GO and KEGG enrichment analyses were performed. Results:The results showed that 4148 significant ChIP-seq peaked in Hct116-derived PGCCs with daughter cells, and 1380 peaked in LoVo-derived PGCCs with daughter cells. Genes with overlapping peaks were then enriched by Gene Ontology [GO], which revealed that these genes participated in various processes including stimulus, cell migration, and cell motility.Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the potential targets involved in metabolic pathways, axon guidance TGF-β signaling pathway, and so on. Conclusions: S100A10 can be modified by SUMOylation in PGCCs and their daughter cells induced by either CoCl2 or chemotherapeutic drugs. SUMO1-modified S100A10 can translocate to the nucleus and regulate the expression of ARHGEF18, PTPRN2, and DEFA3 to promote the proliferation, migration, and invasion of PGCCs and their daughter cells, which may contribute to the poor prognosis in patients with cancer. The discovery of detailed mechanisms of the S100A10 SUMOylation, such as the specific lysine sites involved in SUMOylation and which SUMO E3 ligase regulates the SUMOylation of S100A10 requires further study.
2021-06-07 | GSE176231 | GEO
Project description:We developed an approach to rapidly eliminate the subgroup of sensory neurons expressing the heat-gated cation channel TRPV1 from dissociated rat sensory ganglia using agonist treatment followed by density centrifugation. To identify transcripts predomintly expressed in TRPV1-positive neurons, we compared the transcriptome of all cells within sensory ganglia versus all cells without TRPV1 expressing neurons using RNA-Seq. Four replicate experiments with RNA from DRG neurons of one rat per experiment were performed. Dissociated neurons were split up in three parts, treated with solvent DMSO (0.1%), casaicin (10 µM), or RTX (100 nM) for 30 min followed by gradient centrifugation. RNA was extracted from the remaining pellet containing either all cells or all cells without TRPV1-positive neurons.
2015-05-12 | E-GEOD-59727 | biostudies-arrayexpress
Project description:Genome wide localization of SUMO1 and SUMO2/3 proteins revealed an asscociation of SUMO proetins with active chromatin. SUMO proteins are enriched at super enhancers and enhancers and SUMOylation regulates a subset of these super enhancers. Super enhancers regulated by SUMOylation were enriched for transcription factor TFAP2C and SUMOylation negatively regulates TFAP2C localization to enhancers and super enhancers. Proteomics and ChIP-PCR at MYC SE suggests that chromatin bound TFAP2C recruits histone deacetylation complexes that increases upon SAE2 knockdown. Conversely, SUMOylation promoted TFAP2C asscociation with pre-mRNA splicing machinery components. Taken together, our study revealed a critical role of SUMOylation in chromatin modification through an AP-2 family of transcription factor, TFAP2C and a potential role of TFAP2C in pre-mRNA splicing.
2024-04-13 | GSE171816 | GEO
Project description:Genome wide localization of SUMO1 and SUMO2/3 proteins revealed an asscociation of SUMO proetins with active chromatin. SUMO proteins are enriched at super enhancers and enhancers and SUMOylation regulates a subset of these super enhancers. Super enhancers regulated by SUMOylation were enriched for transcription factor TFAP2C and SUMOylation negatively regulates TFAP2C localization to enhancers and super enhancers. Proteomics and ChIP-PCR at MYC SE suggests that chromatin bound TFAP2C recruits histone deacetylation complexes that increases upon SAE2 knockdown. Conversely, SUMOylation promoted TFAP2C asscociation with pre-mRNA splicing machinery components. Taken together, our study revealed a critical role of SUMOylation in chromatin modification through an AP-2 family of transcription factor, TFAP2C and a potential role of TFAP2C in pre-mRNA splicing.
2024-04-13 | GSE171804 | GEO
Project description:Vampire bats and snakes have taken thermosensation to the extreme by developing specialized systems for detecting infrared radiation. As such, these creatures provide a window into the molecular and genetic mechanisms underlying evolutionary tuning of thermoreceptors in a species or cell type specific manner. In each case, robust thermal sensitivity likely reflects specialized anatomical features of infrared sensing pit organs, as well as intrinsic heat sensitivity of trigeminal nerve fibers that innervate these structures. Here we show that vampire bats use a molecular strategy involving alternative splicing of the TRPV1 gene to generate a channel specifically within trigeminal ganglia that has a reduced thermal activation threshold. Selective expression of splicing factors in trigeminal, but not dorsal root ganglia, together with unique organization of the vampire bat TRPV1 gene underlies this mechanism of sensory adaptation. Comparative genomic analysis of the TRPV1 locus supports phylogenetic relationships within the proposed Pegasoferae clade of mammals. Gene expression measurements implicate a TRPV1 splice isoform as the heat-sensitive channel in vampire bats
2011-08-04 | E-GEOD-28243 | biostudies-arrayexpress