ArticleJournal of experimental & clinical cancer research : CR2017
Upregulation of DARS2 by HBV promotes hepatocarcinogenesis through the miR-30e-5p/MAPK/NFAT5 pathway.
Article in Journal of experimental & clinical cancer research : CR, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 76 citations in OpenAlex.
- DARS2 Promotes Tumorigenesis and Metastasis by Activating PI3K/Akt/GSK-3β/β-Catenin Signaling Pathway in Breast Cancer.The Kaohsiung journal of medical sciences · 2026Article
- Integration of machine learning-based screening approaches and single-cell sequencing technique to identify cancer stemness genes associated with radiotherapy resistance in lung adenocarcinoma.Discover oncology · 2026Article
- A multi-omics prognostic model of cuproptosis affects the prognosis of stomach adenocarcinoma.Clinical epigenetics · 2025Article
- Quantitative proteomic analysis unveils a critical role of VARS1 in hepatocellular carcinoma aggressiveness through the modulation of MAGI1 expression.Molecular cancer · 2025Article
- DARS2 Promotes Bladder Cancer Progression by Enhancing PINK1-Mediated Mitophagy.International journal of biological sciences · 2025Article
- NFAT5: a stress-related transcription factor with multiple functions in health and disease.Cell stress · 2025Review
- Epigenetic modification of hepatitis B virus infection and related hepatocellular carcinoma.Virulence · 2024Review
- Targeted degradation of extracellular mitochondrial aspartyl-tRNA synthetase modulates immune responses.Nature communications · 2024Article
- Genetic variation is a key determinant of chromatin accessibility and drives differences in the regulatory landscape of C57BL/6J and 129S1/SvImJ mice.Nucleic acids research · 2024Article
- Psilostachyin C reduces malignant properties of hepatocellular carcinoma cells by blocking CREBBP-mediated transcription of GATAD2B.Functional & integrative genomics · 2024Article
- Article
- Rel Family Transcription Factor NFAT5 Upregulates COX2 via HIF-1α Activity in Ishikawa and HEC1a Cells.International journal of molecular sciences · 2024Article
- A comparative analysis of TonEBP conditional knockout mouse models reveals inter-dependency between compartments of the intervertebral disc.Development (Cambridge, England) · 2024Article
- Article
- MicroRNA (let-7b-5p)-targeted DARS2 regulates lung adenocarcinoma growth by PI3K/AKT signaling pathway.Oncology research · 2024Article
- DARS2 promotes the occurrence of lung adenocarcinoma via the ERK/c-Myc signaling pathway.Thoracic cancer · 2023Article
- Differentially expressed non-coding RNAs and their regulatory networks in liver cancer.Heliyon · 2023Review
- Aminoacyl-tRNA Synthetase-based Prognosis Model and Exploration of Potential Mechanisms in Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2023Article
- DARS2 overexpression is associated with PET/CT metabolic parameters and affects glycolytic activity in lung adenocarcinoma.Journal of translational medicine · 2023Article
- NFAT5 Restricts Bovine Herpesvirus 1 Productive Infection in MDBK Cell Cultures.Microbiology spectrum · 2023Article
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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
backgroundInfection with the hepatitis B virus (HBV) is closely associated with the development of hepatocellular carcinoma (HCC). The osmoregulatory transcription factor nuclear factor of activated T-cells 5 (NFAT5) has been shown to play an important role in the development of many types of human cancers. The role of NFAT5 in HBV-associated HCC has never previously been investigated.
methodsWe compared expression profiles of NFAT5, DARS2 and miR-30e-5p in HCC samples, adjacent nontumor tissues and different hepatoma cell lines by quantitative real-time polymerase chain reaction and /or Western blot. Clinical data of HCC patients for up to 80 months were analyzed. The regulatory mechanisms upstream and convergent downstream pathways of NFAT5 in HBV-associated HCC were investigated by ChIP-seq, MSP, luciferase report assay and bioinformation anaylsis.
resultsWe first found that higher levels of NFAT5 expression predict a good prognosis, suggesting that NFAT5 is a potential tumor-suppressing gene, and verified that NFAT5 promotes hepatoma cell apoptosis and inhibits cell growth in vitro. Second, our results showed that HBV could suppress NFAT5 expression by inducing hypermethylation of the AP1-binding site in the NFAT5 promoter in hepatoma cells. In addition, HBV also inhibited NFAT5 through miR-30e-5p targeted MAP4K4, and miR-30e-5p in turn inhibited HBV replication. Finally, we demonstrated that NFAT5 suppressed DARS2 by directly binding to its promoter. DARS2 was identified as an HCC oncogene that promotes HCC cell cycle progression and inhibits HCC cell apoptosis.
conclusionHBV suppresses NFAT5 through the miR-30e-5p/mitogen-activated protein kinase (MAPK) signaling pathway upstream of NFAT5 and inhibits the NFAT5 to enhance HCC tumorigenesis via the downstream target genes of DARS2.
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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.