Effect of FABP5 silencing or inhibition on gene expression of Huh7 human hepatoma cells after 48 hours
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE228430 | GEO | 2024/02/17
REPOSITORIES: GEO
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Project description:Effect of FABP5 silencing or inhibition on gene expression of Huh7 human hepatoma cells after 48 hours
| PRJNA949675 | ENA
Project description:Abstract Objective: Osteoarthritis (OA) is accompanied by severe and debilitating pain that current analgesics are unable to fully alleviate. A multitude of signaling molecules, pathways, and cells have been identified as regulators of OA pain. Fatty acid binding protein 5 (FABP5) regulates pain in other disease states and we hypothesized that it is involved in the regulation of OA pain. Design: This was a combined clinical and pre-clinical study. Human synovial and osteochondral tissues collected during total knee arthroplasty were subjected to immunohistochemical analyses to identify the spatial expression patterns of FAB5, COX1, COX2, and macrophages. In addition, synovial specimens were cultured the presence and absence of SBFI-103, a selective FABP5 inhibitor, and cytokines and chemokines levels were measured. The rat monoiodoacetate (MIA) model of OA was then enlisted to evaluate the efficacy of SBFI-103 in alleviating OA pain. Finally, RNAseq was performed to identify alterations in synovial gene expression in vehicle and SBFI-103 treated MIA rats. Results: FABP5 expression was present in clinical OA tissues, with higher expression seen higher grade OA and no apparent differences between genders. Furthermore, FABP5 staining colocalized with CD14+ cells, indicating a macrophage origin of FABP5. Synovial specimens secreted CCL2, IL6, IL8, CXCL1, MIF, and Serpin E1 in vitro and treatment with SBFI-103 attenuated CCL2, IL6, IL8, and CXCL1, but not MIF and Serpin E1. Twenty-eight days after MIA injection, rats exhibited histological joint degradation and significant incapacitance. Ketoprofen treatment partially reduced incapacitance and naproxen had no effect; however, SBFI-103 showed a dose dependent alleviation of incapacitance that was independent of cannabinoid or PPARα receptor activity. RNAseq analyses identified differential expression of >6,000 transcripts compared to contralateral controls in vehicle treated rats and only 513 after SBFI-103 treatment. Notably, CCL2, CCL7, CCL9, and CXCL1were upregulated in vehicle treated rats, but not those treated with SBFI-103, and this was confirmed with qPCR. Conclusions: Our results show that FABP5 is upregulated in clinical and preclinical OA tissues and that its inhibition lowers pronociceptive signaling and reduces OA pain, indicating that FABP5 inhibitors may constitute a novel class of analgesics to treat OA.
2022-12-31 | GSE221957 | GEO
Project description:Prostate cancer (PCa) remains the second leading cause of cancer-related deaths in the United States. Fatty acid-binding protein 5 (FABP5), a member of a class of intracellular lipid transporters, promotes PCa progression via enhanced lipid metabolism and trafficking of lipid ligands. Previous work from our group has shown that the small molecule FABP5 inhibitors based on the truxillic-acid monoester (TAMEs) scaffold reduce PCa growth. In the current study, we demonstrate that the third-generation FABP5 inhibitor SBFI-1143 significantly inhibited the viability and proliferation of PCa cells by arresting cells at the G0/G1 and G2/M phases of the cell cycle and inducing apoptosis and cell death compared to 1st and 2nd generation inhibitors. Stinkingly, SBFI-1143 efficiently inhibited the growth of PCa spheroids compared to its predecessor, SBFI-103. RNA sequencing and Gene Set Enrichment Analysis (GSEA) demonstrated that SBFI-1143 more effectively suppressed the activity of pathways involved in cell cycle progression, cell cycle division, and chromosome organization, while upregulated genes associated with the endoplasmic reticulum (ER) stress, responses to the topologically incorrect folded proteins, and regulating apoptosis compared to the SBFI-103. We further show that SBFI-1143 inhibits oxidative phosphorylation, a process on which PCa depends during cancer initiation and progression. Notably, SBFI-1143 treatment downregulated genes attributed to the subpopulation of PCa cells characterized by the lineage plasticity-related signature leading to trans-differentiation, recurrence, and poor cancer prognosis. Our findings demonstrate that SBFI-1143 significantly modifies the transcriptomic landscape of PCa and may serve as a potentially effective therapeutic option for PCa.
2025-12-17 | GSE297941 | GEO
Project description:Prostate cancer (PCa) remains the second leading cause of cancer-related deaths in the United States. Fatty acid-binding protein 5 (FABP5), a member of a class of intracellular lipid transporters, promotes PCa progression via enhanced lipid metabolism and trafficking of lipid ligands. Previous work from our group has shown that the small molecule FABP5 inhibitors based on the truxillic-acid monoester (TAMEs) scaffold reduce PCa growth. In the current study, we demonstrate that the third-generation FABP5 inhibitor SBFI-1143 significantly inhibited the viability and proliferation of PCa cells by arresting cells at the G0/G1 and G2/M phases of the cell cycle and inducing apoptosis and cell death compared to 1st and 2nd generation inhibitors. Stinkingly, SBFI-1143 efficiently inhibited the growth of PCa spheroids compared to its predecessor, SBFI-103. RNA sequencing and Gene Set Enrichment Analysis (GSEA) demonstrated that SBFI-1143 more effectively suppressed the activity of pathways involved in cell cycle progression, cell cycle division, and chromosome organization, while upregulated genes associated with the endoplasmic reticulum (ER) stress, responses to the topologically incorrect folded proteins, and regulating apoptosis compared to the SBFI-103. We further show that SBFI-1143 inhibits oxidative phosphorylation, a process on which PCa depends during cancer initiation and progression. Notably, SBFI-1143 treatment downregulated genes attributed to the subpopulation of PCa cells characterized by the lineage plasticity-related signature leading to trans-differentiation, recurrence, and poor cancer prognosis. Our findings demonstrate that SBFI-1143 significantly modifies the transcriptomic landscape of PCa and may serve as a potentially effective therapeutic option for PCa.
2025-12-17 | GSE309891 | GEO
Project description:Prostate cancer (PCa) remains the second leading cause of cancer-related deaths in the United States. Fatty acid-binding protein 5 (FABP5), a member of a class of intracellular lipid transporters, promotes PCa progression via enhanced lipid metabolism and trafficking of lipid ligands. Previous work from our group has shown that the small molecule FABP5 inhibitors based on the truxillic-acid monoester (TAMEs) scaffold reduce PCa growth. In the current study, we demonstrate that the third-generation FABP5 inhibitor SBFI-1143 significantly inhibited the viability and proliferation of PCa cells by arresting cells at the G0/G1 and G2/M phases of the cell cycle and inducing apoptosis and cell death compared to 1st and 2nd generation inhibitors. Stinkingly, SBFI-1143 efficiently inhibited the growth of PCa spheroids compared to its predecessor, SBFI-103. RNA sequencing and Gene Set Enrichment Analysis (GSEA) demonstrated that SBFI-1143 more effectively suppressed the activity of pathways involved in cell cycle progression, cell cycle division, and chromosome organization, while upregulated genes associated with the endoplasmic reticulum (ER) stress, responses to the topologically incorrect folded proteins, and regulating apoptosis compared to the SBFI-103. We further show that SBFI-1143 inhibits oxidative phosphorylation, a process on which PCa depends during cancer initiation and progression. Notably, SBFI-1143 treatment downregulated genes attributed to the subpopulation of PCa cells characterized by the lineage plasticity-related signature leading to trans-differentiation, recurrence, and poor cancer prognosis. Our findings demonstrate that SBFI-1143 significantly modifies the transcriptomic landscape of PCa and may serve as a potentially effective therapeutic option for PCa.
2025-12-17 | GSE297940 | GEO
Project description:Purpose: Mouse BMDM is the universal cell type of studying innate immunity. This study was designed to analyze LPS induced innate immune response and the gene expression in FABP5 KO BMDMs with overexpression of FABP5 WT or FABP5 C127S. Methods: FABP5 KO BMDMs were nucleofected with 5 μg pXJ40-3xFlag-FABP5 WT or C127S plasmid using the Amaxa Mouse Macrophage Nucleofector Kit (Lonza, VPA-1009) following the manufacturer’s instructions. Replace medium 6 hours post Nucleofection and add 500 ng/mL LPS to the fresh medium. 24 hours after treatment, harvest cells by using GenElute Single Cell RNA Purification Kit (Sigma, RNB300) and perform RNA-seq. Then mRNA profiles of these samples were generated by high-throughput sequencing analysis, using Illumina NovaSeq6000. And the differential mRNA profiles were analyzed. Results: mRNA profiles were analyzed, and differential expression profiles were compared. Conclusions: Our study demonstrated the transcriptional profiles of FABP5 KO BMDMs with overexpression of FABP5 WT or FABP5 C127S upon LPS treatment, with biologic replicates, generated by RNA-seq technology.
2021-11-01 | GSE182238 | GEO
Project description:The initiation and maintenance of pain involves complex neuroimmune interactions, with myeloid cell output finetuning the balance between pronociceptive and antinociceptive signaling. Fatty acid binding protein 5 (FABP5) is a lipid chaperone whose inhibition produces antinociceptive effects in models of inflammatory pain. While FABP5 is highly expressed in myeloid cells that are recruited to sites of inflammation, the contribution of myeloid FABP5 to nociception is unknown. Utilizing myeloid-specific FABP5 conditional knockout (cKO) mice, we demonstrate that FABP5+ myeloid cells infiltrate into the paw following the onset of carrageenan-induced inflammation. However, myeloid cell recruitment was unaffected by FABP5 deletion. FABP5 cKO were characterized by attenuated development of inflammatory thermal hyperalgesia, which was observed throughout the experimental time course and was evident in both sexes. Transcriptomic profiling of myeloid cells obtained from carrageenan injected paws identified numerous differentially expressed genes between FABP5 cKO mice and Flox controls. Notably, FABP5 cKO myeloid cells featured elevated expression of interleukin-10 (IL-10), consistent with previous findings demonstrating that FABP5 deletion polarizes myeloid cells towards an M2-like anti-inflammatory phenotype. Collectively, this study ascribes a new role to myeloid FABP5 in pain modulation and provides additional evidence that the regulation of nociception by FABP5 involves distinct mechanisms across multiple anatomical loci and cell populations.
2025-11-07 | GSE298388 | GEO
Project description:Hepatitis C virus (HCV) infection is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. HCV can be sensed by host innate immunity to induce expression of interferons (IFNs) and a number of antiviral effectors. HCV-encoded NS3/4 serine protease can subvert host innate immune responses by cleaving MAVS, a critical adaptor protein in the RLR-mediated IFN signaling. To study innate immunity in the context of HCV infection, we constructed Huh7-MAVSR cells which express a mutant MAVS resistant to NS3/4A cleavage. HCV infection induces robust IFN response in Huh7-MAVSR cells, providing a cellular system to study antiviral innate immune response against HCV infection. To analyze host innate antiviral effectors against HCV infection, we performed an mRNA microarray analysis in the HCV-infected Huh7-MAVSR cells.
2018-02-08 | GSE110312 | GEO
Project description:Background: Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate the biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanism of FABP5 in GC are still unclear. Aim: In this study, we aimed to evaluate the clinical and biological function of FABP5 in GC. Methods: We assessed FABP5 expression using immunohistochemical analysis of 79 GC patients and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq) analyses. Results: Elevated FABP5 expression was closely related to poor outcomes, and ectopic expression of FABP5 promoted GC cell proliferation, invasion, migration, and carcinogenicity, suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokine–cytokine receptor-interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies combining FABP5-targeted drugs with immunotherapeutics. Conclusion: These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.
2023-12-31 | GSE218422 | GEO
Project description:The hypoxia response pathway enables adaptation to oxygen deprivation. It is mediated by hypoxia-inducible factors (HIF), which promote metabolic reprogramming, erythropoiesis, angiogenesis and tissue remodeling. This has led to the successful development of HIF-inducing drugs for treating anemia and some of these molecules have now reached the market. However, and because high levels of HIFs are frequently associated to tumor growth, poor prognosis and drug resistance in different types of cancer and in particular hepatocellular carcinoma (HCC), there is concerns that HIF-inducing drugs could promote cancer development. We therefore analyzed in detail the effects of the HIF-inducing drug Molidustat on Huh7 cells, a well-characterized HCC cell line. Combined transcriptomics, proteomics, metabolomics showed that Molidustat reduced cell proliferation, increased the expression of glycolytic enzymes and fragmented the mitochondrial network while decreasing cellular respiration. This profound metabolic remodeling was associated with an improved usage of pyruvate to overcome the inhibition of mitochondrial respiration, and a reduced dependence of this organelle on pyrimidine supply. Overall, this study shows that Molidustat increases the metabolic plasticity of Huh7 cells to adapt changes in their microenvironment, arguing for careful monitoring of patients treated with HIF-inducing drugs when at risk of HCC.
2024-07-30 | PXD049964 | Pride