ArticleDiabetologia2020
Obesity-induced reduced expression of the lncRNA ROIT impairs insulin transcription by downregulation of Nkx6.1 methylation.
Article in Diabetologia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.
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Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 46 citations in OpenAlex.
- Identification and characterization of the long non-coding RNA NFIA-AS2 as a novel locus for body mass index in American Indians.International journal of obesity (2005) · 2023Pooled it
- The Impact of lncRNAs in Diabetes Mellitus: A Systematic Review andFrontiers in endocrinology · 2021Pooled it
- CBX4 stabilizes NEUROD1 through SUMO-ubiquitin crosstalk to delay β-cell senescence.Nature communications · 2026Article
- Mesenchymal stem cells receive adaptive islet-derivedScience advances · 2026Article
- Harnessing exosomal long non-coding RNAs as a new frontier for molecular diagnostics and therapeutics in diabetes mellitus.Cell communication and signaling : CCS · 2026Review
- Advances in the Regulation of Lipid Metabolism by Non-Coding RNAs.Animals : an open access journal from MDPI · 2025Review
- The Long Noncoding RNA ΒFaar Promotes White Adipose Tissue Browning and Prevents Diet-Induced Obesity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A review on cell-free RNA profiling: Insights into metabolic diseases and predictive value for bariatric surgery outcomes.Molecular metabolism · 2024Review
- Targeting β-Cell Plasticity: A Promising Approach for Diabetes Treatment.Current issues in molecular biology · 2024Review
- Epigenetic Regulation of Pancreas Development and Function.Advances in anatomy, embryology, and cell biology · 2024Review
- Clinical relevance of circulating non-coding RNAs in metabolic diseases: Emphasis on obesity, diabetes, cardiovascular diseases and metabolic syndrome.Genes & diseases · 2023Review
- Review
- Genome-wide differential expression profiling of long non-coding RNAs in FOXA2 knockout iPSC-derived pancreatic cells.Cell communication and signaling : CCS · 2023Article
- Regulation of Notch1 Signalling by Long Non-Coding RNAs in Cancers and Other Health Disorders.International journal of molecular sciences · 2023Review
- Circular RNA circGlis3 protects against islet β-cell dysfunction and apoptosis in obesity.Nature communications · 2023Article
- LncRNA-mediated DNA methylation: an emerging mechanism in cancer and beyond.Journal of experimental & clinical cancer research : CR · 2022Review
- Insights into the role of long non-coding RNAs in DNA methylation mediated transcriptional regulation.Frontiers in molecular biosciences · 2022Review
- Article
- It's What and When You Eat: An Overview of Transcriptional and Epigenetic Responses to Dietary Perturbations in Pancreatic Islets.Frontiers in endocrinology · 2022Review
- Hypothalamic long noncoding RNA AK044061 is involved in the development of dietary obesity in mice.International journal of obesity (2005) · 2021Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
aims/hypothesisAlthough obesity is a predisposing factor for pancreatic beta cell dysfunction, the mechanisms underlying its negative effect on insulin-secreting cells is still poorly understood. The aim of this study was to identify islet long non-coding RNAs (lncRNAs) involved in obesity-mediated beta cell dysfunction.
methodsRNA sequencing was performed to analyse the islets of high-fat diet (HFD)-fed mice and those of normal chow-fed mice (NCD). The function in beta cells of the selected lncRNA 1810019D21Rik (referred to in this paper as ROIT [regulator of insulin transcription]) was assessed after its overexpression or knockdown in MIN6 cells and primary islet cells, as well as in siRNA-treated mice. Then, RNA pull-down, RNA immunoprecipitation, coimmunoprecipitation and bisulphite sequencing were performed to investigate the mechanism of ROIT regulation of islet function.
resultsROIT was dramatically downregulated in the islets of the obese mice, as well as in the sera of obese donors with type 2 diabetes, and was suppressed by HNF1B. Overexpression of ROIT in MIN6 cells and islets led to improved glucose homeostasis and insulin transcription. Investigation of the mechanism involved showed that ROIT bound to DNA methyltransferase 3a and caused its degradation through the ubiquitin proteasome pathway, which blocked the methylation of the Nkx6.1 promoter. CONCLUSIONS/
interpretationThese findings functionally suggest a novel link between obesity and beta cell dysfunction via ROIT. Elucidating a precise mechanism for the effect of obesity on lncRNA expression will broaden our understanding of the pathophysiological development of diabetes and facilitate the design of better tools for diabetes prevention and treatment. DATA AVAILABILITY: The raw RNA sequencing data are available from the NCBI Gene Expression Omnibus (GEO series accession number GSE139991).
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Registered trials
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