ArticleOncogene2017
LncRNA MEG3 downregulation mediated by DNMT3b contributes to nickel malignant transformation of human bronchial epithelial cells via modulating PHLPP1 transcription and HIF-1α translation.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 2 of them syntheses that pooled it.
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Who cites it
66 citing papers in PubMed, 2 syntheses or guidelines pooled it, 139 citations in OpenAlex.
- Toxic Metal in Plant-Based Therapeutics: Contamination Pathways, Oxidative Stress Induction, and Onset of Disease.TheScientificWorldJournal · 2026Pooled it
- Association between lncRNA GAS5, MEG3, and PCAT-1 Polymorphisms and Cancer Risk: A Meta-Analysis.Disease markers · 2020Pooled it
- Loss of MEG3 promotes migration and invasion of nickel-transformed cells, partially via upregulation of RUNX2.Toxicology and applied pharmacology · 2026Article
- Natural Compounds as Epimodulators in Epithelial Ovarian Cancer.Epigenomes · 2026Review
- The role of long non-coding RNAs in lung cancer metastasis: Molecular mechanisms, pathogenesis and clinical implications.Clinical and translational medicine · 2025Review
- Dysregulation of Long Non-coding RNAs-the Novel lnc in Metal Toxicity and Carcinogenesis.Current environmental health reports · 2024Review
- The strict regulation of HIF-1α by non-coding RNAs: new insight towards proliferation, metastasis, and therapeutic resistance strategies.Cancer metastasis reviews · 2024Review
- Tumorigenesis of basal muscle invasive bladder cancer was mediated by PTEN protein degradation resulting from SNHG1 upregulation.Journal of experimental & clinical cancer research : CR · 2024Article
- Non-coding RNAs and exosomal non-coding RNAs in lung cancer: insights into their functions.Frontiers in cell and developmental biology · 2024Review
- Non-coding RNAs/DNMT3B axis in human cancers: from pathogenesis to clinical significance.Journal of translational medicine · 2023Review
- The role of hypoxia-inducible factor 1 alpha (HIF-1α) modulation in heavy metal toxicity.Archives of toxicology · 2023Review
- Article
- Long Non-Coding RNA MEG3 in Metal Carcinogenesis.Toxics · 2023Review
- Loss of MEG3 contributes to the enhanced migration and invasion in arsenic-induced carcinogenesis through NQO1/FSCN1 pathway.American journal of cancer research · 2023Article
- Novel genetic variants in long non-coding RNA MEG3 are associated with the risk of asthma.PeerJ · 2023Article
- Review
- DNMT1-mediated demethylation of lncRNA MEG3 promoter suppressed breast cancer progression by repressing Notch1 signaling pathway.Cell cycle (Georgetown, Tex.) · 2022Article
- LncRNA in tumorigenesis of non-small-cell lung cancer: From bench to bedside.Cell death discovery · 2022Review
- Loss of MEG3 and upregulation of miR-145 play an important role in the invasion and migration of Cr(VI)-transformed cells.Heliyon · 2022Article
- MARCKSL1-2 reverses docetaxel-resistance of lung adenocarcinoma cells by recruiting SUZ12 to suppress HDAC1 and elevate miR-200b.Molecular cancer · 2022Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Long noncoding RNAs (lncRNAs) are emerging as key factors in various fundamental cellular biological processes, and many of them are likely to have functional roles in tumorigenesis. Maternally expressed gene 3 (MEG3) is an imprinted gene located at 14q32 that encodes a lncRNA, and the decreased MEG3 expression has been reported in multiple cancer tissues. However, nothing is known about the alteration and role of MEG3 in environmental carcinogen-induced lung tumorigenesis. Our present study, for the first time to the best of our knowledge, discovered that environmental carcinogen nickel exposure led to MEG3 downregulation, consequently initiating c-Jun-mediated PHLPP1 transcriptional inhibition and hypoxia-inducible factor-1α (HIF-1α) protein translation upregulation, in turn resulting in malignant transformation of human bronchial epithelial cells. Mechanistically, MEG3 downregulation was attributed to nickel-induced promoter hypermethylation via elevating DNMT3b expression, whereas PHLPP1 transcriptional inhibition was due to the decreasing interaction of MEG3 with its inhibitory transcription factor c-Jun. Moreover, HIF-1α protein translation was upregulated via activating the Akt/p70S6K/S6 axis resultant from PHLPP1 inhibition in nickel responses. Collectively, we uncover that nickel exposure results in DNMT3b induction and MEG3 promoter hypermethylation and expression inhibition, further reduces its binding to c-Jun and in turn increasing c-Jun inhibition of PHLPP1 transcription, leading to the Akt/p70S6K/S6 axis activation, and HIF-1α protein translation, as well as malignant transformation of human bronchial epithelial cells. Our studies provide a significant insight into understanding the alteration and role of MEG3 in nickel-induced lung tumorigenesis.
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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.