ArticleJournal of experimental & clinical cancer research : CR2021
Long non-coding RNA MAPKAPK5-AS1/PLAGL2/HIF-1α signaling loop promotes hepatocellular carcinoma progression.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 93 citations in OpenAlex.
- Non-coding RNAs: modulators of signaling pathways and prognostic biomarkers in digestive system cancer.Molecular cancer · 2026Review
- Exploring the Shared Genetic Architectures Between Primary Open-Angle Glaucoma and Visual Pathway Regions in the Brain.Investigative ophthalmology & visual science · 2025Article
- Liver-specific lncRNAs associated with liver cancers.FEBS open bio · 2025Review
- The Vulpes vulpes montana genome provides insights into high-altitude adaptation mechanisms of the Vulpes species.Communications biology · 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
- Development of a MVI associated HCC prognostic model through single cell transcriptomic analysis and 101 machine learning algorithms.Scientific reports · 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
- CAF-EVs carry lncRNA MAPKAPK5-AS1 into hepatocellular carcinoma cells and promote malignant cell proliferation.Communications biology · 2024Article
- Hyperoxia exposure induces ferroptosis and apoptosis by downregulating PLAGL2 and repressing HIF-1α/VEGF signaling pathway in newborn alveolar typeII epithelial cell.Redox report : communications in free radical research · 2024Article
- Deciphering the nexus between long non-coding RNAs and endoplasmic reticulum stress in hepatocellular carcinoma: biomarker discovery and therapeutic horizons.Cell death discovery · 2024Review
- Exploring the promise of regulator of G Protein Signaling 20: insights into potential mechanisms and prospects across solid cancers and hematological malignancies.Cancer cell international · 2024Review
- Construction of lncRNA- and circRNA-associated ceRNA networks in the prostatic urethra of rats after simulating transurethral laser prostatectomy (TULP).Molecular and cellular biochemistry · 2024Article
- PLAG1 interacts with GPX4 to conquer vulnerability to sorafenib induced ferroptosis through a PVT1/miR-195-5p axis-dependent manner in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2024Article
- OTUD5 promotes the growth of hepatocellular carcinoma by deubiquitinating and stabilizing SLC38A1.Biology direct · 2024Article
- Classification of Long Non-Coding RNAs s Between Early and Late Stage of Liver Cancers From Non-coding RNA Profiles Using Machine-Learning Approach.Bioinformatics and biology insights · 2024Article
- New HCC Subtypes Based on CD8 Tex-Related lncRNA Signature Could Predict Prognosis, Immunological and Drug Sensitivity Characteristics of Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2024Article
- Construction of a prognostic prediction model in liver cancer based on genes involved in integrin cell surface interactions pathway by multi-omics screening.Frontiers in cell and developmental biology · 2024Article
- GATA6-AS1 suppresses epithelial-mesenchymal transition of pancreatic cancer under hypoxia through regulating SNAI1 mRNA stability.Journal of translational medicine · 2023Article
- The role of noncoding RNAs in the tumor microenvironment of hepatocellular carcinoma.Acta biochimica et biophysica Sinica · 2023Review
- PLAGL2 promotes bladder cancer progression via RACGAP1/RhoA GTPase/YAP1 signaling.Cell death & disease · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLong non-coding RNAs (lncRNAs) are widely involved in human cancers' progression by regulating tumor cells' various malignant behaviors. MAPKAPK5-AS1 has been recognized as an oncogene in colorectal cancer. However, the biological role of MAPKAPK5-AS1 in hepatocellular carcinoma (HCC) has not been explored.
methodsQuantitative real-time PCR was performed to detect the level of MAPKAPK5-AS1 in HCC tissues and cell lines. The effects of MAPKAPK5-AS1 on tumor growth and metastasis were assessed via in vitro experiments, including MTT, colony formation, EdU, flow cytometry, transwell assays, and nude mice models. The western blotting analysis was carried out to determine epithelial-mesenchymal transition (EMT) markers and AKT signaling. The interaction between MAPKAPK5-AS1, miR-154-5p, and PLAGL2 were explored by luciferase reporter assay and RNA immunoprecipitation. The regulatory effect of HIF-1α on MAPKAPK5-AS1 was evaluated by chromatin immunoprecipitation.
resultsMAPKAPK5-AS1 expression was significantly elevated in HCC, and its overexpression associated with malignant clinical features and reduced survival. Functionally, MAPKAPK5-AS1 knockdown repressed the proliferation, mobility, and EMT of HCC cells and induced apoptosis. Ectopic expression of MAPKAPK5-AS1 contributed to HCC cell proliferation and invasion in vitro. Furthermore, MAPKAPK5-AS1 silencing suppressed, while MAPKAPK5-AS1 overexpression enhanced HCC growth and lung metastasis in vivo. Mechanistically, MAPKAPK5-AS1 upregulated PLAG1 like zinc finger 2 (PLAGL2) expression by acting as an endogenous competing RNA (ceRNA) to sponge miR-154-5p, thereby activating EGFR/AKT signaling. Importantly, rescue experiments demonstrated that the miR-154-5p/PLAGL2 axis mediated the function of MAPKAPK5-AS1 in HCC cells. Interestingly, we found that hypoxia-inducible factor 1α (HIF-1α), a transcript factor, could directly bind to the promoter to activate MAPKAPK5-AS1 transcription. MAPKAPK5-AS1 regulated HIF-1α expression through PLAGL2 to form a hypoxia-mediated MAPKAPK5-AS1/PLAGL2/HIF-1α signaling loop in HCC.
conclusionsOur results reveal a MAPKAPK5-AS1/PLAGL2/HIF-1α signaling loop in HCC progression and suggest that MAPKAPK5-AS1 could be a potential novel therapeutic target of HCC.
Indexed as
Identifiers
What OpenQuestion holds
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.