Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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RNA-seq of human liver cancer cell line SNU-398 treated with a novel sulfane sulfur donor (PSCP) against untreated controls

ABSTRACT: This study elucidates the molecular mechanisms underlying the antitumor effects of a novel sulfane sulfur donor compound on hepatocellular carcinoma (HCC) cells using RNA sequencing analysis. While sulfane sulfur has emerged as a crucial signaling molecule with therapeutic potential in cancer treatment, its precise mechanisms of action remain to be fully elucidated. We synthesized a novel sulfane sulfur donor (persulfided cysteine precursor, PSCP) that exhibits potent inhibitory effects on HCC cells. Through comprehensive RNA-seq analysis of PSCP-treated HCC cells versus controls, we uncovered a complex regulatory mechanism involving mitochondrial damage, AMPK activation, and p53-mediated cellular responses, including both proliferation inhibition and apoptosis induction. Our findings demonstrate that PSCP exerts its anti-HCC effects through a mitochondrial damage-AMPK-p53 signaling cascade, with p53 serving as a key mediator that both suppresses cell proliferation and promotes apoptosis. These results provide novel insights into the antitumor mechanisms of sulfane sulfur compounds and highlight their therapeutic potential in HCC treatment.  Treatment group: SNU398 HCC cells treated with 200 μM PSCP for 24 hours  Control group: SNU398 cells treated with vehicle control  Three-four biological replicates per group  mRNA extraction using TRIzol reagent (Invitrogen, MD, USA)  Sequencing performed by Biomarker Technologies (Guangzhou, China)  Sequencing platform: Oxford Nanopore Technologies (Oxford, UK)  Data analysis conducted using BMK_Cloud platform

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Homo sapiens

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PROVIDER: E-MTAB-14578 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Hepatocellular carcinoma is one of the most frequently diagnosed cancers in the world. Post-translational modifications (PTMs) play an essential role during cancer development. Phosphorylation is an important PTMs. To identify the modifications of phosphorylation in HCC, a multiplexed tandem mass tag (TMT) approach combined with LC−MS/MS was used. A total of 4,780 phosphorylated sites distributed on 2,209 proteins were identified and quantified, including 74 and 459 phosphorylated up-regulated and down-regulated proteins, respectively. Bio-informatic analysis revealed the differences and commonalities between HCC and normal tissues. Gene ontology enrichment analysis provided the information on biological processes, molecular functions, cellular components, and sub-cellular localizations. Protein domains enrichment of differentially expressed proteins were analyzed by InterPro database. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed the pathways that could potentially be involved in HCC. Integrative analysis of the functions, pathways, motifs of phosphorylated peptides, protein domains and protein interactions could establish a profile of phosphoproteome of HCC, which may contribute to identify new biomarkers for diagnosis and prognosis for HCC and novel therapeutic targets for HCC treatment.Hepatocellular carcinoma is one of the most frequently diagnosed cancers in the world. Post-translational modifications (PTMs) play an essential role during cancer development. Phosphorylation is an important PTMs. To identify the modifications of phosphorylation in HCC, a multiplexed tandem mass tag (TMT) approach combined with LC−MS/MS was used. A total of 4,780 phosphorylated sites distributed on 2,209 proteins were identified and quantified, including 74 and 459 phosphorylated up-regulated and down-regulated proteins, respectively. Bio-informatic analysis revealed the differences and commonalities between HCC and normal tissues. Gene ontology enrichment analysis provided the information on biological processes, molecular functions, cellular components, and sub-cellular localizations. Protein domains enrichment of differentially expressed proteins were analyzed by InterPro database. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed the pathways that could potentially be involved in HCC. Integrative analysis of the functions, pathways, motifs of phosphorylated peptides, protein domains and protein interactions could establish a profile of phosphoproteome of HCC, which may contribute to identify new biomarkers for diagnosis and prognosis for HCC and novel therapeutic targets for HCC treatment.

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RNA-seq of human liver cancer cell line SNU-398 treated with a novel sulfane sulfur donor (PSCP) against untreated controls

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