{"database":"biostudies-arrayexpress","file_versions":[],"scores":null,"additional":{"submitter":["Russta Fayyazi"],"organism":["Homo sapiens"],"software":["R (R Studio)","Galaxy (usegalaxy.org)"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/E-MTAB-15818"],"description":["The activating signal co-integrator 1 complex subunit 3 (ASCC3), a multifunctional protein, has been implicated as a prognostic marker in several types of cancer. However, mechanisms underlying its prognostic value are not fully understood. Here, we report that ASCC3 promotes sensitivity to chemotherapeutic drugs, such as 5-fluorouracil, cisplatin, and hydroxyurea, in colorectal cancer (CRC) cells, likely in a cancer type dependent manner. Increased chemoresistance resulting from ASCC3 loss is not due to reduced genomic instability as evidenced by enhanced accumulation of DNA damage and micronuclei following exposure to these drugs. RNA-seq analysis reveals that ASCC3 stimulates the expression of gene sets associated with mTORC1 signaling, glycolysis, and protein folding pathways in CRC cells. While promoting the serine biosynthesis pathway, we demonstrate, through extracellular flux assays and stable isotopes tracer analysis, that ASCC3 reprograms energy metabolism, favoring glycolysis over oxidative phosphorylation. Furthermore, we find that ASCC3 is required for PERK production upon ER stress. Impaired PERK production is associated with reduced levels of CHOP and caspase 3 following treatment with 5-fluorouracil, indicating that ASCC3 promotes PERK production to enhance cell death upon chemotherapy. Collectively, our work underscores molecular complexities underlying chemoresistance in the wake of ASCC3 loss in CRC cells."],"repository":["biostudies-arrayexpress"],"sample_protocol":["Nucleic Acid Extraction - Total RNA was extracted with TRIzol and purified using the RNeasy Mini Kit (Qiagen, cat. no. 74106) per manufacturer’s instructions; RNA integrity was confirmed by BioAnalyzer.","Library Construction - Libraries were prepared using the NEBNext® Ultra™ II Directional RNA Library Prep Kit (New England Biolabs) with poly(A) selection, following the manufacturer’s protocol.","Sequencing - Libraries were sequenced on an Illumina NextSeq 2000 (P2 flow cell) in paired-end 2 × 50 bp configuration.","Sample Collection - HCT116 parental (WT) and ASCC3-KO cells were maintained at 37°C with 5% CO₂ in DMEM supplemented with 10% fetal bovine serum, L-glutamine, non-essential amino acids, 100 U/mL penicillin and 0.1 mg/mL streptomycin; cultures were routinely screened for mycoplasma by DAPI staining. Cells were harvested for RNA extraction."],"figure_sub":["Organization","MINSEQE Score","Assays and Data","Processed Data","MAGE-TAB Files"],"data_protocol":["Sequence Alignment - Raw reads were trimmed for adapters and low-quality bases using Cutadapt, then aligned to the hg38 reference genome with HISAT2. Gene-level read counts were generated using featureCounts.","Data Transformation - Counts from featureCounts were normalized using the variance-stabilizing transformation (VST) in DESeq2 (v1.46.0, Bioconductor) to produce the processed expression matrix."],"omics_type":["Unknown","Transcriptomics","Genomics","Proteomics"],"instrument_platform":["NextSeq 2000"],"study_type":["RNA-seq of total RNA"],"species":["Homo sapiens"],"pubmed_authors":["Xu-Dong Zhu","Russta Fayyazi"],"additional_accession":[]},"is_claimable":false,"name":"ASCC3 promotes chemosensitivity in colorectal cancer cells","description":"The activating signal co-integrator 1 complex subunit 3 (ASCC3), a multifunctional protein, has been implicated as a prognostic marker in several types of cancer. However, mechanisms underlying its prognostic value are not fully understood. Here, we report that ASCC3 promotes sensitivity to chemotherapeutic drugs, such as 5-fluorouracil, cisplatin, and hydroxyurea, in colorectal cancer (CRC) cells, likely in a cancer type dependent manner. Increased chemoresistance resulting from ASCC3 loss is not due to reduced genomic instability as evidenced by enhanced accumulation of DNA damage and micronuclei following exposure to these drugs. RNA-seq analysis reveals that ASCC3 stimulates the expression of gene sets associated with mTORC1 signaling, glycolysis, and protein folding pathways in CRC cells. While promoting the serine biosynthesis pathway, we demonstrate, through extracellular flux assays and stable isotopes tracer analysis, that ASCC3 reprograms energy metabolism, favoring glycolysis over oxidative phosphorylation. Furthermore, we find that ASCC3 is required for PERK production upon ER stress. Impaired PERK production is associated with reduced levels of CHOP and caspase 3 following treatment with 5-fluorouracil, indicating that ASCC3 promotes PERK production to enhance cell death upon chemotherapy. Collectively, our work underscores molecular complexities underlying chemoresistance in the wake of ASCC3 loss in CRC cells.","dates":{"release":"2025-11-15T00:00:00Z","modification":"2025-11-15T02:02:22.982Z","creation":"2025-10-22T14:22:10.818Z"},"accession":"E-MTAB-15818","cross_references":{"ENA":["ERP182708"],"EFO":["EFO_0002944","EFO_0004170","EFO_0009653","EFO_0004917","EFO_0005518","EFO_0003816","EFO_0004184"]}}