ArticleCell death & disease2021
HIF-1α-activated long non-coding RNA KDM4A-AS1 promotes hepatocellular carcinoma progression via the miR-411-5p/KPNA2/AKT pathway.
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 43 papers.
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Who cites it
43 citing papers in PubMed, 69 citations in OpenAlex.
- Salidroside Attenuates High-Altitude Hypoxic Myocardial Injury Through Modulation of Oxidative Stress and AKT/GSK-3β Signaling Pathways.Applied biochemistry and biotechnology · 2026Article
- Homeobox B13 activates the hypoxia-inducible factor 1 pathway through histone lactylation thereby reprogramming lipid metabolism and promoting sorafenib resistance in hepatocellular carcinoma.Journal of cell communication and signaling · 2026Article
- DNASE1L3 functions as a significant metastatic suppressor by attenuating MYH9/β-catenin/c-Jun/LncRNA-KDM4A-induced E-cadherin ubiquitination degradation in nasopharyngeal carcinoma.Cellular & molecular biology letters · 2026Article
- HDAC5 stabilization by tubeimoside I suppresses cervical cancer metastasis via inhibiting H3K27ac/KPNA2 axis.British journal of cancer · 2026Article
- Integrative transcriptomic analysis reveals miR-26a-5p downregulation and a potential predictive gene signature for the progression of metabolic liver disease.Frontiers in cell and developmental biology · 2026Article
- MiR-20a-5p Inhibits Bladder Cancer Proliferation and Migration by Targeting KPNA2.Journal of cellular and molecular medicine · 2025Article
- A novel hypoxia-induced lncRNA, SZT2-AS1, boosts HCC progression by mediating HIF heterodimerization and histone trimethylation under a hypoxic microenvironment.Cell death and differentiation · 2025Article
- Utilizing liquid-liquid biopolymer regulators to predict the prognosis and drug sensitivity of hepatocellular carcinoma.Biology direct · 2025Article
- Crosstalk between hypoxia-inducible factor (HIF) and lncRNAs in digestive tumors: from molecular mechanisms to clinical translation.Frontiers in cell and developmental biology · 2025Review
- Deciphering the nexus between long non-coding RNAs and endoplasmic reticulum stress in hepatocellular carcinoma: biomarker discovery and therapeutic horizons.Cell death discovery · 2024Review
- Article
- MicroRNA-411-5p alleviates lipid deposition in metabolic dysfunction-associated steatotic liver disease by targeting the EIF4G2/FOXO3 axis.Cellular and molecular life sciences : CMLS · 2024Article
- Article
- TGF-β1-Induced LINC01094 promotes epithelial-mesenchymal transition in hepatocellular carcinoma through the miR-122-5p/TGFBR2-SAMD2-SMAD3 Axis.Functional & integrative genomics · 2024Article
- Advances and challenges of exosome-derived noncoding RNAs for hepatocellular carcinoma diagnosis and treatment.Biochemistry and biophysics reports · 2024Review
- Ethanol responsive lnc171 promotes migration and invasion of HCC cells via mir-873-5p/ZEB1 axis.BMC cancer · 2024Article
- The emerging roles of lysine-specific demethylase 4A in cancer: Implications in tumorigenesis and therapeutic opportunities.Genes & diseases · 2024Review
- Novel molecular hepatocellular carcinoma subtypes and RiskScore utilizing apoptosis-related genes.Scientific reports · 2024Article
- Unraveling the underlying pathogenic factors driving nonalcoholic steatohepatitis and hepatocellular carcinoma: an in-depth analysis of prognostically relevant gene signatures in hepatocellular carcinoma.Journal of translational medicine · 2024Article
- Exosome prospects in the diagnosis and treatment of non-alcoholic fatty liver disease.Frontiers in medicine · 2024Review
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is the most common type of liver cancer with poor clinical outcomes. Long non-coding RNAs (lncRNAs) are extensively involved in the tumorigenesis and progression of HCC. However, more investigations should be carried out on novel lncRNAs and their effects on HCC. Here we identified a novel lncRNA KDM4A-AS1, which was aberrantly overexpressed in HCC tissues, associated with unfavorable clinical features and poor prognosis of patients. KDM4A-AS1 promoted HCC cell proliferation, migration, and invasion in vitro and contributed to HCC growth and lung metastasis in vivo. Mechanistically, KDM4A-AS1 was inversely modulated by miR-411-5p at the post-transcriptional level and facilitated Karyopherin α2 (KPNA2) expression by competitively binding miR-411-5p, thereby activating the AKT pathway. KPNA2 silencing, miR-411-5p overexpression, and AKT inhibitor (MK2206) consistently reversed KDM4A-AS1-enhanced proliferation, mobility, and EMT of HCC cells. KDM4A-AS1 was identified as a novel hypoxia-responsive gene and transactivated by hypoxia-inducible factor 1α (HIF-1α) in HCC cells. In turn, KDM4A-AS1 regulated HIF-1α expression through the KPNA2/AKT signaling pathway. Hence, this study revealed a novel hypoxia-responsive lncRNA, KDM4A-AS1, which contributed to HCC growth and metastasis via the KDM4A-AS1/KPNA2/HIF-1α signaling loop. Our findings provide a promising prognostic and therapeutic target for HCC.
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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.