ArticleOncotarget2016
A MALAT1/HIF-2α feedback loop contributes to arsenite carcinogenesis.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- A meta-analysis of the clinicopathological significance of the lncRNA MALAT1 in human gastric cancer.Frontiers in oncology · 2023Pooled it
- Role of Hypoxia-Associated Long Noncoding RNAs in Cancer Chemo-Therapy Resistance.International journal of molecular sciences · 2025Review
- Dysregulation of Long Non-coding RNAs-the Novel lnc in Metal Toxicity and Carcinogenesis.Current environmental health reports · 2024Review
- Review
- Cross talk between genetics and biochemistry in the pathogenesis of hepatocellular carcinoma.Hepatology forum · 2024Review
- Role of Lnc-RNAs in the Pathogenesis and Development of Diabetic Retinopathy.International journal of molecular sciences · 2023Review
- The role of long non-coding RNA ANRIL in the development of atherosclerosis.Non-coding RNA research · 2022Review
- Review
- Long non-coding RNAs and microRNAs as crucial regulators in cardio-oncology.Cell & bioscience · 2022Review
- Dysregulations of long non-coding RNAs - The emerging "lnc" in environmental carcinogenesis.Seminars in cancer biology · 2021Review
- The role of hypoxia-induced long noncoding RNAs (lncRNAs) in tumorigenesis and metastasis.Biomedical journal · 2021Review
- Review
- CircRNA-100284 activates aurora kinase B by inducing methylation of HSP70 via microRNA-217 to promote proliferation of bladder cancer cells.Journal of cancer research and clinical oncology · 2021Article
- Hypoxia-InducedFrontiers in oncology · 2021Article
- The emerging landscape of long non-coding RNAs in hepatocellular carcinoma.International journal of clinical and experimental pathology · 2021Review
- Role of non-coding-RNAs in response to environmental stressors and consequences on human health.Redox biology · 2020Review
- Long-Noncoding RNA (lncRNA) in the Regulation of Hypoxia-Inducible Factor (HIF) in Cancer.Non-coding RNA · 2020Review
- Signaling in and out: long-noncoding RNAs in tumor hypoxia.Journal of biomedical science · 2020Review
- Long noncoding RNA MALAT1 inhibits the apoptosis and autophagy of hepatocellular carcinoma cell by targeting the microRNA-146a/PI3K/Akt/mTOR axis.Cancer cell international · 2020Article
- Regulatory Networks of LncRNA MALAT-1 in Cancer.Cancer management and research · 2020Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Arsenic is well established as a human carcinogen, but the molecular mechanisms leading to arsenic-induced carcinogenesis are complex and elusive. It is also not known if lncRNAs are involved in arsenic-induced liver carcinogenesis. We have found that MALAT1, a non-coding RNA, is over-expressed in the sera of people exposed to arsenite and in hepatocellular carcinomas (HCCs), and MALAT1 has a close relation with the clinicopathological characteristics of HCC. In addition, hypoxia-inducible factor (HIF)-2α is up-regulated in HCCs, and MALAT1 and HIF-2α have a positive correlation in HCC tissues. During the malignant transformation of human hepatic epithelial (L-02) cells induced by a low concentration (2.0 μM) of arsenite, MALAT1 and HIF-2α are increased. In addition, arsenite-induced MALAT1 causes disassociation of the von Hippel-Lindau (VHL) protein from HIF-2α, therefore, alleviating VHL-mediated HIF-2α ubiquitination, which causes HIF-2α accumulation. In turn, HIF-2α transcriptionally regulates MALAT1, thus forming a positive feedback loop to ensure expression of arsenite-induced MALAT1 and HIF-2α, which are involved in malignant transformation. Moreover, MALAT1 and HIF-2α promote the invasive and metastatic capacities of arsenite-induced transformed L-02 cells and in HCC-LM3 cells. The capacities of MALAT1 and HIF-2α to promote tumor growth are validated in mouse xenograft models. In mice, arsenite induces an inflammatory response, and MALAT1 and HIF-2α are over-expressed. Together, these findings suggest that the MALAT1/HIF-2α feedback loop is involved in regulation of arsenite-induced malignant transformation. Our results not only confirm a novel mechanism involving reciprocal regulation between MALAT1 and HIF-2α, but also expand the understanding of the carcinogenic potential of arsenite.
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