ArticleCell death & disease2021
MRPS31 loss is a key driver of mitochondrial deregulation and hepatocellular carcinoma aggressiveness.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- The Proteome of Bone Marrow Multipotent Mesenchymal Stromal Cells Undergoes Significant Alterations in Acute Leukemia Patients at the Onset and During Treatment.International journal of molecular sciences · 2026Article
- MRPL13 sustains mitochondrial integrity and MAPK-associated aggressiveness in esophageal squamous cell carcinoma.Cancer cell international · 2026Article
- A mitochondrial function-based prognostic model for hepatocellular carcinoma uncovers MRPS15 as a key driver of tumor progression through oxidative phosphorylation.Translational cancer research · 2026Article
- Transcriptome and plasma proteome analyses identify susceptibility genes and proteins for alcohol-related hepatocellular carcinoma.Human genomics · 2026Article
- MRPL37 promotes hepatocellular carcinoma progression through modulating mitochondrial energy metabolism.iScience · 2025Article
- Integrated multi-omics analysis identifies DARS2, MRTO4, and MRPL37 as novel biomarkers and potential therapeutic targets for bladder cancer.Discover oncology · 2025Article
- MRPL13 enhances mitochondrial function and promotes tumor progression in ovarian cancer by inhibiting mPTP opening via SLC25A6.Cell death & disease · 2025Article
- MRPL21-PARP1 axis promotes cisplatin resistance in head and neck squamous cell carcinoma by inhibiting autophagy through the PI3K/AKT/mTOR signaling pathway.Journal of experimental & clinical cancer research : CR · 2025Article
- Mitochondrial Ribosomal Protein S17 Silencing Inhibits Proliferation and Invasiveness of Lung Cancer Cells.Journal of cancer prevention · 2025Article
- Precision Prediction of Alzheimer's Disease: Integrating Mitochondrial Energy Metabolism and Immunological Insights.Journal of molecular neuroscience : MN · 2025Article
- Mitochondrial ribosomal proteins: potential targets for cancer prognosis and therapy.Frontiers in oncology · 2025Review
- Peptidomic analysis reveals novel peptide PDLC promotes cell proliferation in hepatocellular carcinoma via Ras/Raf/MEK/ERK pathway.Scientific reports · 2024Article
- New insights into the role of mitochondrial metabolic dysregulation and immune infiltration in septic cardiomyopathy by integrated bioinformatics analysis and experimental validation.Cellular & molecular biology letters · 2024Article
- Article
- MRPL48 is a novel prognostic and predictive biomarker of hepatocellular carcinoma.European journal of medical research · 2023Article
- Multi-omics analysis of MRPL-13 as a tumor-promoting marker from pan-cancer to lung adenocarcinoma.Aging · 2023Article
- MRPL12 Acts as A Novel Prognostic Biomarker Involved in Immune Cell Infiltration and Tumor Progression of Lung Adenocarcinoma.International journal of molecular sciences · 2023Article
- Extracellular vesicle small RNA cargo discriminates non-cancer donors from pediatric B-lymphoblastic leukemia patients.Frontiers in oncology · 2023Article
- Article
- Mitoribosomal defects aggravate liver cancer via aberrant glycolytic flux and T cell exhaustion.Journal for immunotherapy of cancer · 2022Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deregulated mitochondrial energetics is a metabolic hallmark of cancer cells. However, the causative mechanism of the bioenergetic deregulation is not clear. In this study, we show that somatic copy number alteration (SCNA) of mitoribosomal protein (MRP) genes is a key mechanism of bioenergetic deregulation in hepatocellular carcinoma (HCC). Association analysis between the genomic and transcriptomic profiles of 82 MRPs using The Cancer Genome Atlas-Liver HCC database identified eight key SCNA-dependent MRPs: MRPS31, MRPL10, MRPL21, MRPL15, MRPL13, MRPL55, and DAP3. MRPS31 was the only downregulated MRP harboring a DNA copy number (DCN) loss. MRPS31 loss was associated specifically with the DCN losses of many genes on chromosome 13q. Survival analysis revealed a unique dependency of HCC on the MRPS31 deficiency, showing poor clinical outcome. Subclass prediction analysis using several public classifiers indicated that MRPS31 loss is linked to aggressive HCC phenotypes. By employing hepatoma cell lines with SCNA-dependent MRPS31 expression (JHH5, HepG2, Hep3B, and SNU449), we demonstrated that MRPS31 deficiency is the key mechanism, disturbing the whole mitoribosome assembly. MRPS31 suppression enhanced hepatoma cell invasiveness by augmenting MMP7 and COL1A1 expression. Unlike the action of MMP7 on extracellular matrix destruction, COL1A1 modulated invasiveness via the ZEB1-mediated epithelial-to-mesenchymal transition. Finally, MRPS31 expression further stratified the high COL1A1/DDR1-expressing HCC groups into high and low overall survival, indicating that MRPS31 loss is a promising prognostic marker. SIGNIFICANCE: Our results provide new mechanistic insight for mitochondrial deregulation in HCC and present MRPS31 as a novel biomarker of HCC malignancy.
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