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YTHDC1 lactylation promotes RCC progression by regulating phase-separation to enhance the stabilities of BCL2 and E2F2 mRNAs

ABSTRACT: To obtain the global landscape of lactylation in hypoxia-treated RCC cells, we treated cells with 24 h hypoxia to induce maximum amount of hyperlactylated proteins and performed proteome and lactylome detection upon ACHN cells. Presented here is the raw data for the proteome.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Kidney Cancer

SUBMITTER: yuangui tang

LAB HEAD: Junfang Zheng

PROVIDER: PXD052772 | Pride | 2025-07-18

REPOSITORIES: Pride

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			Action	DRS
	FA026LQ_C_1_Slot2-15_1_5094.d.zip	Other
	FA026LQ_C_2_Slot2-15_1_5095.d.zip	Other
	FA026LQ_C_3_Slot2-15_1_5096.d.zip	Other
	FA026LQ_H24_1_Slot2-16_1_5098.d.zip	Other
	FA026LQ_H24_2_Slot2-16_1_5099.d.zip	Other

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YTHDC1 lactylation promotes RCC progression by regulating phase-separation to enhance the stabilities of BCL2 and E2F2 mRNAs

Project description:To obtain the global landscape of lactylation in hypoxia-treated RCC cells, we treated cells with 24 h hypoxia to induce maximum amount of hyperlactylated proteins and performed proteome and lactylome detection upon ACHN cells. Presented here is the raw data for the lactylome.

2025-07-18 | PXD053029 | Pride

Analysis of lactylome refines key molecular reprogramming mechanisms during oil production in Nannochloropsis oceanica

Project description:Lysine lactylation as a type of posttranslational modifications (PTMs) is recently associated with chromatin remodeling and gene transcription, but lysine lactylation of histone and non-histone proteins has not yet been studied in Nannochloropsis oceanica. To examine the prevalence and function of lactylation in N. oceanica, protein lactylation modification profiles were tracked after nitrogen deprivation for three days using 4D label-free proteome method. Under nitrogen deprivation (ND) and nitrogen repletion (NR) cultivation conditions, we mapped lactylome of proliferating microalgal cells.

2024-07-03 | PXD038775 | Pride

Lactylation of nucleus pulposus cells

Project description:Nucleus pulposus (NP) resides in hypoxic microenvironment due to the avascular structure of intervertebral disc (IVD). Intracellular lactate drives lysine lactylation (Kla) as a newly epigenetic modification. However, the impact of Kla on NPCs remains unknown. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we showed a global lactylome profiling on NPCs cultured in normoxia and hypoxia environment and found that 3510 lactylation sites on 1052 proteins in NPCs on non-histone proteins. Moreover, there are 18 proteins with 129 Kla sites exclusively detected in the normoxia group, and 117 Kla sites in 27 proteins were specific in hypoxia group. Together, our dates reveals that Kla plays an important role in regulating cellular metabolism and may contribute to IDD progression.

2025-05-06 | PXD048244 | Pride

Effects of moderate intensity exercise on liver metabolism in mice based on multi-omics analysis

Project description:Background: Physical exercise is beneficial to keep physical and mental health. The molecular mechanisms underlying exercise are still worth exploring. Methods: The healthy adult mice after six weeks of moderate-intensity exercise (experimental group) and sedentary mice (control group) were used to perform transcriptomic, proteomic, lactylation modification, and metabolomics analysis. In addition, gene sets related to hypoxia, glycolysis, and fatty acid metabolism were used to aid in the screening of hub genes. The mMCP-counter was employed to evaluate infiltration of immune cells in murine liver tissues. Results: Transcriptomics analysis revealed 82 intersection genes related to hypoxia, glycolysis, and fatty acid metabolism. Proteomics and lactylation modification analysis identified 577 proteins and 141 differentially lactylation modification proteins. By overlapping 82 intersection genes with 577 differentially expressed proteins and 141 differentially lactylation modification proteins, three hub genes (Aldoa, Acsl1, and Hadhb) were obtained. The immune infiltration analysis revealed a decreased score for monocytes/macrophages and an increased score for endothelial cells in the experimental group. Then, 459 metabolites in positive mode and 181 metabolites in negative mode were identified. The “Metabolic pathways” (mmu01100) was a common pathway between intersection genes-enriched pathways and metabolites-enriched pathways. Conclusion: These findings highlight the pivotal roles of hub genes in the glycolysis and fatty acid metabolism under the context of chronic exercise.

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GABA regulates IL-1β production in macrophages

Project description:Neurotransmitters have been well-documented to determine immune cell fates; however, whether and how γ-amino butyric acid (GABA) shapes the function of innate immune cells is still obscure. Here, we demonstrated that GABA orchestrates macrophage maturation and inflammation. GABA treatment during macrophage maturation inhibits interleukin (IL)-1β production from inflammatory macrophages. Mechanistically, GABA enhances succinate-FAD-lysine demethylase1 (LSD1) signaling to regulate the histone demethylation of Bcl2l11 and Dusp2, lowering the formation of NLRP3-ASC-Caspase-1 complex. Meanwhile, GABA-succinate axis lowers succinylation of mitochondrial proteins to promote mitochondrial oxidative phosphorylation (OXPHOS). We also found that GABA alleviates the LPS-induced sepsis as well as high-fat diet-induced obesity in mice. Our study proves that GABA is potential in lessening the pro-inflammatory macrophage responses associating with metabolic reprogramming and protein succinylation, thus providing a strategy for treating macrophage-related inflammatory diseases.

2022-11-29 | PXD037901 | Pride

Crotonylomics sequencing of human non small cell lung cancer cell lines

Project description:Crotonylation is a crotonyl-coenzyme A (CoA)-mediated post-translational modification best known for its roles in epigenetic regulation. Histone lysine crotonylation (Kcr) has been reported to be involved in tumor-related biological functions such as DNA damage repair and immune infiltration. Here we find that abnormal reduction of histone Kcr significantly correlates with a poor response to epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in in-house-established drug-resistant models of lung cancer cell lines, and in cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models. The crotonyl-CoA-producing enzyme ACSS2 is the key regulator of the resistance-related change of crotonylation. Quantitative crotonylomic, transcriptomic and epigenomic analyses reveal that EGFR-TKI resistance is accompanied by reduced levels of histone 3 lysine 56 crotonylation (H3K56cr) on chromatin, which inhibits transcription of HNF1A and activates the PI3K/AKT signaling pathway. Studies of patient-derived organoids (PDOs) and resistant lung cancer CDX and PDX models treated with a novel histone decrotonylase (HDCR) inhibitor, S67, demonstrate that up-regulation of H3K56cr sensitizes cells to the effect of EGFR-TKIs. These findings uncover the role of histone Kcr in resistance to EGFR-TKIs and suggest a new combination therapy in lung cancer.

2025-09-22 | PXD053030 | Pride

Comprehensive ubiquitomics characterization identify biomarkers of liver cancer subtypes

Project description:Hepatocellular carcinoma (HCC) has been widely studied at multi-omics level, but little is known about its specific ubiquitination, a major post-translational modification (PTM). In this study, we performed the ubiquitomics data collected from 85 HCC tumors and 18 adjacent normal tissues (ANTs) to establish the ubiquitomic profiles of HCC and reveal tumor-associated characteristics with prognosis and clinical outcomes. Ubiquitomic based stratification of HCC revealed three subtypes related to different clinical and molecular features, suggesting ubiquitomics have the potential to further understand the relationship between ubiquitination levels of proteins and different molecular and clinical features of HCC patients. XAD1—XAD18 --- HCC adjacent normal tissues XC1—XC85--- HCC tumor tissues

2025-04-07 | PXD047211 | Pride

Characterization of protein lactylation in relation to cardiac metabolic reprogramming in neonatal mouse hearts

Project description:In mammals, the neonatal heart regenerates within a short time after birth, but adults lack this ability. We have shown that metabolic reprogramming is critical for cardiomyocyte proliferation in the neonatal heart. Herein, we revealed that cardiac metabolic reprogramming could be regulated by altering global protein lactylation. 4D label-free proteomics and Kla omics were performed in postnatal Day 1 (P1), 5 (P5), and 7 (P7) mouse hearts, 2297 Kla sites from 980 proteins were identified, and 1262 Kla sites from 409 proteins were quantified. Functional clustering analysis of proteins with altered Kla sites revealed that the proteins were mainly involved in metabolic processes. The Kla levels in several fatty acid oxidation-related proteins showed high expression at P5, while glycolysis and cell cycle-related proteins were sustainedly decreased from P1-P7. Furthermore, we verified the Kla levels of several differentially modified proteins, including ACAT1, ACADL, PKM and NPM1, by coimmunoprecipitation and Western blotting. Overall, we reported the first comprehensive Kla map in the neonatal mouse heart, which will aid in understanding the regulatory network of metabolic reprogramming and cardiac regeneration.

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Succinylation proteome analysis of Cd-exposed Neuro-2a cells

Project description:Cadmium is a neurotoxic compound which induces cognitive alterations similar to those produced by Alzheimer's disease (AD). Autophagic flux impairment is a hallmark in Cd-induced AD-like pathology. However, the underlying mechanism remains obscure. In these study, Neuro-2a cells were exposed to different concentrations of Cd (1, 2, and 4 μM) for 72 h, and C57 mice (8 week) were orally administered Cd for 12 weeks. Chronic Cd exposure inhibited autophagosome-lysosome fusion and impaired lysosomal function, thereby contributing to defects in autophagic clearance and subsequently leading to APP accumulation and nerve cell death. Mechanistically, proteomic analysis coupled with Ingenuity Pathway Analysis identified the crucial key target molecule in Cd-impaired autophagic flux. Four-dimensional label-free succinylation quantitative proteomics were performed in Neuro-2a cells with and without 4 μM CdCl2 treatment for 72h. Then, vital molecules and crucial succinylation sites were identified. Moreover, the function and important role of the resulting molecule with crucial succinylation site were determined. These results may thus open an avenue for therapeutic intervention in chronic Cd-induced AD-like pathology.

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Project description:To examine the mechanisms during oil production and integrate analysis of lactylation in N. oceanica, protein expression profiles were tracked after nitrogen deprivation for three days using 4D label-free proteome method. Under nitrogen deprivation (ND) and nitrogen repletion (NR) cultivation conditions, we mapped proteome of proliferating microalgal cells.

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