ArticleCell communication and signaling : CCS2021
miR-1250-5p is a novel tumor suppressive intronic miRNA hypermethylated in non-Hodgkin's lymphoma: novel targets with impact on ERK signaling and cell migration.
Article in Cell communication and signaling : CCS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed, 14 citations in OpenAlex.
- Integrated bioinformatics and deep learning (MLP) approach reveals a novel five miRNA prognostic signature in uveal melanoma.Scientific reports · 2025Article
- Screening and molecular mechanism research on bile microRNAs associated with chemotherapy efficacy in perihilar cholangiocarcinoma.iScience · 2024Article
- Hsa_circ_0010023 promotes the development of papillary thyroid carcinoma by sponging miR-1250-5p.Endocrine · 2024Article
- Epigenetic alterations and advancement of lymphoma treatment.Annals of hematology · 2024Review
- Functional Screen for microRNAs Suppressing Anchorage-Independent Growth in Human Cervical Cancer Cells.International journal of molecular sciences · 2022Article
- Development and performance evaluation of TaqMan real-time fluorescence quantitative methylation specific PCR for detecting methylation level of PER2.Molecular biology reports · 2022Article
- Epigenetic Silencing of Tumor Suppressor lncRNAGenes · 2022Article
- MiR-204-5p Alleviates Neuropathic Pain by Targeting BRD4 in a Rat Chronic Constrictive Injury Model.Journal of pain research · 2022Article
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3 authors at 2 institutions in 2 countries.
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Abstract
backgroundmiR-1250 is localised to the second intron of AATK at chromosome 17q25. As a CpG island is present at the putative promoter region of its host gene, AATK, we postulated that the intronic miR-1250-5p is a tumor suppressor miRNA co-regulated with its host gene, AATK, by promoter DNA methylation in non-Hodgkin's lymphoma (NHL).
methodsAATK/miR-1250 methylation was studied in healthy controls, including ten normal peripheral blood buffy coats and eleven normal tonsils, ten lymphoma cell lines, and 120 primary lymphoma samples by methylation-specific PCR (MSP). The expression of miR-1250-5p and AATK was investigated by quantitative real-time PCR. Tumor suppressor properties of miR-1250-5p were demonstrated by over-expression of precursor miR-1250-5p in lymphoma cells. The target of miR-1250-5p was verified by luciferase reporter assay.
resultsAATK/miR-1250 methylation was absent in healthy peripheral blood and tonsils, but detected in five (50%) NHL cell lines. AATK/miR-1250 methylation correlated with repression of miR-1250-5p and AATK in NHL cell lines. In completely methylated SU-DHL-6 and SUP-T1 cells, treatment with 5-AzadC led to promoter demethylation and re-expression of both miR-1250-5p and AATK. In primary lymphoma samples, AATK/miR-1250 was frequently methylated in B-cell lymphoma (n = 41, 44.09%) and T-cell lymphoma (n = 9, 33.33%) with a comparable frequency (P = 0.318). In SU-DHL-6 and SU-DHL-1 cells, restoration of miR-1250-5p resulted in decreased cellular proliferation by MTS assay, increased cell death by trypan blue staining and enhanced apoptosis by annexin V-PI assay. Moreover, MAPK1 and WDR1 were verified as direct targets of miR-1250-5p by luciferase assay. In 39 primary NHLs, miR-1250-5p expression was shown to be inversely correlated with each of MAPK1 (P = 0.05) and WDR1 (P = 0.031) by qRT-PCR. Finally, in SU-DHL-1 cells, overexpression of miR-1250-5p led to repression of MAPK1 and WDR1 at both transcript and protein levels, with downregulation of phospho-ERK2 by Western-blotting and inhibition of SDF-1-dependent cell migration by transwell assay.
conclusionsmiR-1250-5p is a novel tumor suppressive intronic miRNA co-regulated and silenced by promoter DNA methylation of its host gene AATK in NHL. MAPK1 and WDR1 are novel miR-1250-5p direct targets rendering inhibition of MAPK/ERK signaling and SDF-1-dependent cell migration, hence implicated in survival and dissemination of lymphoma. Video Abstract.
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