ArticleCell death and differentiation2017
The lncRNA HOTAIRM1 regulates the degradation of PML-RARA oncoprotein and myeloid cell differentiation by enhancing the autophagy pathway.
Article in Cell death and differentiation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 1 of them a synthesis that pooled it.
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124 citing papers in PubMed, 1 synthesis or guideline pooled it, 247 citations in OpenAlex.
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- Multiomic single-cell perturbation screens reveal critical lncRNA regulators of senescence.Nature aging · 2026Article
- Autophagy and Lipid Metabolism as a Therapeutic Target for Overcoming Drug Resistance in Acute Myeloid Leukemia.Life (Basel, Switzerland) · 2026Review
- The Epigenetic Angle in the Precision Medicine Era for Blood Disorder Advancements.Sub-cellular biochemistry · 2026Review
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- Crosstalk between noncoding RNAs and autophagy in renal cell carcinoma: Deciphering molecular pathways and therapeutic prospects.Cancer cell international · 2025Review
- Targeting USP2 induces degradation of PML-RARα with or without drug-resistant mutations in acute promyelocytic leukemia.Acta biochimica et biophysica Sinica · 2025Article
- Biomolecules Interacting with Long Noncoding RNAs.Biology · 2025Review
- Role of MicroRNAs in Acute Myeloid Leukemia.Genes · 2025Review
- Interplay between LncRNAs and autophagy-related pathways in leukemia: mechanisms and clinical implications.Medical oncology (Northwood, London, England) · 2025Review
- Long noncoding RNAs in acute myeloid leukemia: biomarkers, prognostic indicators, and treatment potential.Cancer cell international · 2025Review
- Exploring the hidden hot world of long non-coding RNAs in thermophilic fungus using a robust computational pipeline.Scientific reports · 2024Article
- Multiple roles of arsenic compounds in phase separation and membraneless organelles formation determine their therapeutic efficacy in tumors.Journal of pharmaceutical analysis · 2024Review
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- Exosome-encapsulated lncRNA HOTAIRM1 contributes to PMScience China. Life sciences · 2024Article
- Blockade of the lncRNA-DOT1L-LAMP5 axis enhances autophagy and promotes degradation of MLL fusion proteins.Experimental hematology & oncology · 2024Article
- The Roles of Autophagy-related miRNAs in Gynecologic Tumors: A Review of Current Knowledge for Possible Targeted Therapy.Current molecular medicine · 2024Review
- Endocrine nuclear receptors and long non‑coding RNAs reciprocal regulation in cancer (Review).International journal of oncology · 2024Review
- LncRNA HOTAIRM1 promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by targeting miR-152-3p/ETS1 axis.Molecular biology reports · 2023Article
64 more citing papers are in PubMed but not listed here.
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8 authors at 1 institution in 1 country.
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Abstract
Increasing evidence has indicated that long noncoding RNAs (lncRNAs) are of great importance in different cell contexts. However, only a very small number of lncRNAs have been experimentally validated and functionally annotated during human hematopoiesis. Here, we report an lncRNA, HOTAIRM1, which is associated with myeloid differentiation and has pivotal roles in the degradation of oncoprotein PML-RARA and in myeloid cell differentiation by regulating autophagy pathways. We first revealed that HOTAIRM1 has different variants that are expressed at different levels in cells and that the expression pattern of HOTAIRM1 is closely related to that of the PML-RARA oncoprotein in acute promyelocytic leukemia (APL) patients. We further revealed that the downregulation of HOTAIRM1 could inhibit all-trans retinoic acid (ATRA) -induced degradation of PML-RARA in APL cells and repress the process of differentiation from promyelocytic to granulocytic cells. More importantly, we found that HOTAIRM1 regulates autophagy and that autophagosome formation was inhibited when HOTAIRM1 expression was reduced in the cells. Finally, through the use of a dual luciferase activity assay, AGO2 RNA immunoprecipitation and RNA pull-down, HOTAIRM1 was revealed to act as a microRNA sponge in a pathway that included miR-20a/106b, miR-125b and their targets ULK1, E2F1 and DRAM2. We constructed a human APL-ascites SCID mouse model to validate the function of HOTAIRM1 and its regulatory pathway in vivo. This is the first report showing that a lncRNAs regulates autophagy and the degradation of the PML-RARA oncoprotein during the process of myeloid cell differentiation blockade, suggesting that lncRNAs may be the potential therapeutic targets for leukemia.
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