ArticleCell death & disease2023
The microprotein encoded by exosomal lncAKR1C2 promotes gastric cancer lymph node metastasis by regulating fatty acid metabolism.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 50 citations in OpenAlex.
- Functions of exosome-derived noncoding RNA-encoded polypeptides/proteins in human diseases.Genes & diseases · 2027Review
- Noncoding RNA encoded peptides in tumors from discovery to mechanism and clinical translation.iScience · 2026Review
- Article
- The identity crisis of cryptic lncRNAs: when non-coding RNAs translate into small peptides.The EMBO journal · 2026Review
- Dual roles of lactylation modification in gastric cancer: Crosstalk between metabolic reprogramming and epigenetic regulation (Review).Oncology reports · 2026Review
- Long non-coding RNAs in the exosomal network: dual roles and clinical implications in cancer.Animal cells and systems · 2026Review
- Exosome-orchestrated network in gastric cancer: mechanisms, immune regulation, biomarkers and therapeutic vehicles.Frontiers in cell and developmental biology · 2026Review
- TRIM26 deficiency drives gastric cancer lymph node metastasis via TGF-β signaling activation and modulates gemcitabine response.Frontiers in cell and developmental biology · 2026Article
- Role of Aldo-Keto reductase family 1 member C in cancer progression: a special focus on the role of AKR1C1 in pancreatic cancer.Medical oncology (Northwood, London, England) · 2025Article
- Long non-coding RNAs in cancer glycolysis and metabolism: mechanisms and translational opportunities.Cell death & disease · 2025Review
- EPDR1 promotes gastric cancer progression via STAT3-mediated fatty acid metabolic reprogramming.European journal of medical research · 2025Article
- Clinical relevance of extracellular vesicles in cancer - therapeutic and diagnostic potential.Nature reviews. Clinical oncology · 2025Review
- Micropeptides in the oncological dark matter: decoding their roles in tumor progression and therapy resistance.Journal of translational medicine · 2025Review
- Novel therapeutic strategies for targeting fatty acid oxidation in cancer.Biomarker research · 2025Review
- NPR1 Promotes Lipid Droplet Lipolysis to Enhance Mitochondrial Oxidative Phosphorylation and Fuel Gastric Cancer Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Abnormal mitochondrial structure and function in brown adipose tissue of SLC35A4-MP knockout mice.Science advances · 2025Article
- Comparative analysis of engineered-exosome delivered si-HER2 and trastuzumab in the treatment of HER2-positive gastric cancer.Investigational new drugs · 2025Article
- LncRNA-Encoded Micropeptides: Expression Validation, Translational Mechanisms, and Roles in Cellular Metabolism.International journal of molecular sciences · 2025Review
- Unraveling the advances of non-coding RNAs on the tumor microenvironment: innovative strategies for cancer therapies.Journal of translational medicine · 2025Review
- Beyond the Transcript: Translating Non-Coding RNAs and Their Impact on Cellular Regulation.Cancers · 2025Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lymph node metastasis (LNM) is the prominent route of gastric cancer dissemination, and usually leads to tumor progression and a dismal prognosis of gastric cancer. Although exosomal lncRNAs have been reported to be involved in tumor development, whether secreted lncRNAs can encode peptides in recipient cells remains unknown. Here, we identified an exosomal lncRNA (lncAKR1C2) that was clinically correlated with lymph node metastasis in gastric cancer in a VEGFC-independent manner. Exo-lncAKR1C2 secreted from gastric cancer cells was demonstrated to enhance tube formation and migration of lymphatic endothelial cells, and facilitate lymphangiogenesis and lymphatic metastasis in vivo. By comparing the metabolic characteristics of LN metastases and primary focuses, we found that LN metastases of gastric cancer displayed higher lipid metabolic activity. Moreover, exo-lncAKR1C2 encodes a microprotein (pep-AKR1C2) in lymphatic endothelial cells and promotes CPT1A expression by regulating YAP phosphorylation, leading to enhanced fatty acid oxidation (FAO) and ATP production. These findings highlight a novel mechanism of LNM and suggest that the microprotein encoded by exosomal lncAKR1C2 serves as a therapeutic target for advanced gastric cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.