ArticleClinical epigenetics2019
Epigenetic silencing of miR-340-5p in multiple myeloma: mechanisms and prognostic impact.
Article in Clinical epigenetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- Deciphering epigenetic crosstalk in multiple myeloma pathogenesis and treatment.Clinical epigenetics · 2026Review
- Advancing the therapeutic effectiveness of paclitaxel in chronic lymphocytic leukemia through the simultaneous inhibition of NOTCH1 and SF3B1.Cancer cell international · 2025Article
- Case Report: Unveiling the role of genetic abnormalities in myelomatous pleural effusion: a case of IgG lambda-type multiple myeloma.Frontiers in oncology · 2025Article
- GTF2E2 downregulated by miR-340-5p inhibits the malignant progression of glioblastoma.Cancer gene therapy · 2023Article
- Pan-cancer analysis of oncogenic TNFAIP2 identifying its prognostic value and immunological function in acute myeloid leukemia.BMC cancer · 2022Article
- Inhibition of RNA Binding in SND1 Increases the Levels of miR-1-3p and Sensitizes Cancer Cells to Navitoclax.Cancers · 2022Article
- Review
- Knockdown of XIST up-regulates 263294miR-340-5p to relieve myocardial ischaemia-reperfusion injury via inhibiting cyclin D1.ESC heart failure · 2022Article
- One Omics Approach Does Not Rule Them All: The Metabolome and the Epigenome Join Forces in Haematological Malignancies.Epigenomes · 2021Review
- Epigenetic Regulation of microRNAs in Cancer: Shortening the Distance from Bench to Bedside.International journal of molecular sciences · 2021Review
- Deep Learning Feature Extraction Approach for Hematopoietic Cancer Subtype Classification.International journal of environmental research and public health · 2021Article
- miR-340: A multifunctional role in human malignant diseases.International journal of biological sciences · 2021Review
- Long Non-Coding RNAs: Potential Biomarkers and Targets for Hepatocellular Carcinoma Therapy and Diagnosis.International journal of biological sciences · 2021Review
- miR-744-5p Inhibits Multiple Myeloma Proliferation, Epithelial Mesenchymal Transformation and Glycolysis by Targeting SOX12/Wnt/β-Catenin Signaling.OncoTargets and therapy · 2021Article
- Overexpression of microRNA-340-5p Ameliorates Inflammatory Response and Intracellular Survival ofInfection and drug resistance · 2021Article
- The Role of miRNAs 340-5p, 92a-3p, and 381-3p in Patients with Endometriosis: A Plasma and Mesenchymal Stem-Like Cell Study.BioMed research international · 2021Article
- Clinical significance of miR-1180-3p in hepatocellular carcinoma: a study based on bioinformatics analysis and RT-qPCR validation.Scientific reports · 2020Article
- Frequent upregulation of G9a promotes RelB-dependent proliferation and survival in multiple myeloma.Experimental hematology & oncology · 2020Article
- DNMT1 recruited by EZH2-mediated silencing of miR-484 contributes to the malignancy of cervical cancer cells through MMP14 and HNF1A.Clinical epigenetics · 2019Article
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Authors and funding
6 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundmiR-340-5p, localized to 5q35, is a tumor suppressor miRNA implicated in multiple cancers. As a CpG island is present at the putative promoter region of its host gene, RNF130, we hypothesized that the intronic miR-340-5p is a tumor suppressor miRNA epigenetically silenced by promoter DNA methylation of its host gene in multiple myeloma.
resultsBy pyrosequencing-confirmed methylation-specific PCR, RNF130/miR-340 was methylated in 8/15 (53.3%) myeloma cell lines but not normal plasma cells. Methylation correlated inversely with the expression of both miR-340-5p and RNF130. In completely methylated WL-2 and RPMI-8226R cells, 5-AzadC treatment led to demethylation and re-expression of miR-340-5p. In primary samples, RNF130/miR-340 methylation was detected in 4 (22.2%) monoclonal gammopathy of undetermined significance, 15 (23.8%) diagnostic myeloma, and 7 (23.3%) relapsed myeloma. RNF130/miR-340 methylation at diagnosis was associated with inferior overall survival (median 27 vs. 68 months; P = 3.944E-5). In WL-2 cells, overexpression of miR-340-5p resulted in reduced cellular proliferation [MTS, P = 0.002; verified in KMS-12-PE (P = 0.002) and RPMI-8226R (P = 2.623E-05) cells], increased cell death (trypan blue, P = 0.005), and enhanced apoptosis by annexin V-PI staining. Moreover, by qRT-PCR, overexpression of miR-340-5p led to repression of both known targets (CCND1 and NRAS) and bioinformatically predicted targets in MAPK signaling (MEKK1, MEKK2, and MEKKK3) and apoptosis (MDM4 and XIAP), hence downregulation of phospho-ERK1/2 and XIAP by Western blot. Furthermore, by qRT-PCR, in CD138-sorted primary samples (n = 37), miR-340-5p and XIAP were inversely correlated (P = 0.002). By luciferase assay, XIAP was confirmed as a direct target of miR-340-5p via targeting of the distal but not proximal seed region binding site.
conclusionsCollectively, tumor-specific methylation-mediated silencing of miR-340-5p is likely an early event in myelomagenesis with adverse survival impact, via targeting multiple oncogenes in MAPK signaling and apoptosis, thereby a tumor suppressive miRNA in myeloma.
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