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Long noncoding rna IDI2-AS1 modulates the expression of interleukin 5 in human cells

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 2025年 761卷 151733页

作者： Endo, Ryuki Kurisu, Miyu Tani, Hidenori Yokohama Univ Pharm Dept Hlth Pharm 601 Matano Totsuka Yokohama 2450066 Japan

Long noncoding rnas (lncrnas) have emerged as critical regulators of gene expression, influencing a wide range of biological processes. In this study, we investigate the regulatory role of the lncrna IDI2-AS1 in the immune response. Our previous observations demonstrated that IDI2-AS1 expression is downregulated in A549 cells upon exposure to lipopolysaccharide (LPS) and poly I:C, which mimic bacterial and viral infections, respectively. Here, we analyzed the expression changes of 13 immune response genes following sirna-mediated knockdown of IDI2-AS1 in A549 cells. Notably, our results revealed a significant and selective upregulation of interleukin 5 (IL5) mrna expression, which increased approximately 60-fold, along with a corresponding similar to 70-fold increase in IL5 protein levels. These findings suggest a novel regulatory mechanism in which IDI2-AS1 functions as a suppressor of IL5 expression under normal conditions. During simulated bacterial or viral infections, the downregulation of IDI2-AS1 appears to initiate a rapid and robust increase in IL5 expression. Given the pivotal role of IL5 in allergic inflammation and eosinophil regulation, the IDI2-AS1-IL5 axis may represent an important pathway in the immune response to pathogenic challenges. This study provides new insights into the intricate interplay between lncrnas and cytokine gene regulation in innate immunity, potentially offering novel therapeutic targets for immune-related disorders.

关键词： noncoding rna Lncrna IDI2-AS1 Interleukin 5

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noncoding rna as potential therapeutics to rescue mitochondrial dysfunction in cardiovascular diseases

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American Journal of Physiology - Heart and Circulatory Physiology 2025年第4期328卷 H846-H864页

作者： Alabere, Hafsat O. Taylor, Andrew D. Miller, Brianna R. Nohoesu, Remi Nicoletti, Roxy Mogus, Joshua Meadows, Ethan M. Hollander, John M. Division of Exercise Physiology West Virginia University School of Medicine Morgantown WV United States Mitochondria Metabolism & Bioenergetics Working Group West Virginia University School of Medicine Morgantown WV United States Department of Biochemistry and Molecular Medicine West Virginia University School of Medicine Morgantown WV United States Department of Physiology Pharmacology and Toxicology West Virginia University School of Medicine Morgantown WV United States

noncoding rnas (ncrnas) are critical regulators of mitochondrial function in cardiovascular diseases. Several studies have explored the manipulation of ncrnas in mitochondrial dysfunction in different cardiovascular disease contexts, however, there is a dearth of information on the exploration of these noncoding rnas as actual therapeutics to ameliorate cardiovascular diseases. This systematic review examines the roles of various ncrnas in modulating mitochondrial dysfunction across major cardiovascular diseases and how they can be targeted to the mitochondria. A comprehensive literature search was conducted using Web of Science and Scopus databases, following the PRISMA guidelines. Original research articles in the English language, focusing on ncrnas and mitochondrial dysfunction in specific cardiovascular diseases, were eligible for inclusion. A total of 76 studies were included in the systematic review with up to 100 ncrnas identified as therapeutic biomarkers. The identified ncrnas participate in regulating mitochondrial processes including oxidative phosphorylation (OXPHOS), fission/fusion dynamics, apoptosis, and calcium handling in cardiovascular diseases. Mitochondrial targeting moieties including mitochondrial targeting cell-penetrating peptides, mitochondrial targeting liposomes, and aptamers can be conjugated to ncrnas and delivered to the heart via various injection routes including the pericardium or the myocardium. However, significant challenges remain in developing effective delivery methods to modulate these ncrnas in vivo. Copyright © 2025 The Authors.

关键词： cardiovascular disease mitochondria noncoding rna rna therapeutics systematic review

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The human-specific noncoding rna RP11-424G14.1 functions at the intersection of sexually dimorphic pathways in inflammation, senescence, and metabolism

FASEB BIOADVANCES

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FASEB BIOADVANCES 2025年第2期7卷 e1479页

作者： Kennicott, Kameron Liang, Yun Michigan State Univ Dept Physiol & Pharmacol & Toxicol E Lansing MI USA Michigan State Univ Dept Pharmacol & Toxicol E Lansing MI 48824 USA

Sexual dimorphism is a fundamental characteristic of various physiological and pathological processes in humans, including immune responses, senescence, and metabolism. Most studies on the sex bias have focused on sex hormones or female-biased genes, whereas male-biased genetic factors remain understudied. Here, we show that the Y-linked noncoding rna, RP11-424G14.1, is expressed in human male keratinocytes. Microarray study suggests the NF-kappa B pathway as the top biological pathway affected by RP11-424G14.1 knockdown, consistent with known sex differences in inflammation. Additionally, IGFBP3 is identified as the top gene supported by RP11-424G14.1 in male keratinocytes. Conversely, in female keratinocytes, IGFBP3 is the top gene repressed by the X-linked long noncoding rna XIST, suggesting a central role of IGFBP3 in mediating sexual dimorphism. Knockdown of RP11-424G14.1 or IGFBP3 in male keratinocytes inhibits cellular senescence, consistent with increased longevity in females. IGFBP3 expression is dependent on insulin, and metabolomics analysis suggests that RP11-424G14.1 and IGFBP3 regulate acrylcarnitine metabolism. Our study identifies the role of the RP11-424G14.1-IGFBP3 pathway in coordinating sex differences in immunity, senescence, and metabolism. With RP11-424G14.1 being a human-specific genetic element, our study suggests the evolving feature of sexual dimorphisms in biological processes.

关键词： inflammation metabolism noncoding rna senescence sexual dimorphism

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noncoding rna transcription at enhancers and genome folding in cancer

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CANCER SCIENCE 2019年第8期110卷 2328-2336页

作者： Isoda, Takeshi Morio, Tomohiro Takagi, Masatoshi Tokyo Med & Dent Univ Dept Pediat & Dev Biol Tokyo Japan

Changes of nuclear localization of lineage-specific genes from a transcriptionally inert to permissive environment are a crucial step in establishing the identity of a cell. noncoding rna transcription-mediated genome folding and activation of target gene expression have been found in a variety of cell types. noncoding rna ThymoD (thymocyte differentiation factor) transcription at superenhancers is essential for mouse T-cell lineage commitment. The cessation of ThymoD transcription abolishes transcription-mediated demethylation, recruiting looping factors such as the cohesin complex, CCCTC-binding factor (CTCF), ultimately leading to the phenotype of severe combined immunodeficiency and T-cell leukemia/lymphoma. In this review, we describe the functional role of rna polymerase II-mediated transcription at enhancers and in genome folding. We also highlight the involvement of faulty activation or suppression of enhancer transcription and enhancer-promoter interaction in cancer development.

关键词： cancer genome folding noncoding rna ThymoD transcription

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noncoding rna for personalized prostate cancer treatment: utilizing the 'dark matters' of the genome

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PERSONALIZED MEDICINE 2017年第2期14卷 159-169页

作者： Hua, Junjie Lu, Jennifer Isaev, Keren Soares, Fraser Guo, Haiyang Ahmed, Musaddeque He, Housheng Hansen Univ Hlth Network Princess Margaret Canc Ctr Toronto ON Canada Univ Toronto Dept Med Biophys Toronto ON Canada Univ Toronto Dept Lab Med & Pathobiol Toronto ON Canada

Prostate cancer is the most commonly diagnosed cancer in men in western countries, with significant health impact. Clinically, it is complicated with the lack of biomarkers and effective treatments for aggressive disease, particularly castration-resistant prostate cancer. Although we have gained much insight into the biology of prostate cancer through studying protein-coding genes, they represent only a small fraction of our genome. Therefore, it is essential for us to investigate noncoding rnas, which comprise the majority of our transcriptome, in order to achieve a better understanding of prostate cancer and move toward personalized medicine. In this article, we will address recent advancements in our knowledge of noncoding rnas, and discuss the clinical potentials and challenges of different types of noncoding rnas in prostate cancer.

关键词： biomarker noncoding rna personalized medicine prostate cancer therapy

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noncoding rnas and rna-binding proteins: emerging governors of liver physiology and metabolic diseases

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AMERICAN JOUrnaL OF PHYSIOLOGY-CELL PHYSIOLOGY 2022年第4期323卷 C1003-C1017页

作者： Sommerauer, Christian Kutter, Claudia Karolinska Inst Dept Microbiol Tumor & Cell Biol Sci Life Lab Stockholm Sweden

The liver holds central roles in detoxification, energy metabolism, and whole body homeostasis but can develop malignant phenotypes when being chronically overwhelmed with fatty acids and glucose. The global rise of metabolic dysfunction -associated fatty liver disease (MAFLD) is already affecting a quarter of the global population. Pharmaceutical treatment options against different stages of MAFLD do not yet exist, and several clinical trials against hepatic transcription factors and other proteins have failed. However, emerging roles of noncoding rnas, including long (lncrna) and short noncoding rnas (srna), in various cellular processes pose exciting new avenues for treatment interventions. Actions of noncoding rnas mostly rely on interactions with proteins, whereby the noncoding rna fine-tunes protein function in a process termed riboregulation. The developmental stage-, disease stage-, and cell type-specific nature of noncoding rnas harbors enor-mous potential to precisely target certain cellular pathways in a spatiotemporally defined manner. Proteins interacting with rnas can be categorized into canonical or noncanonical rna-binding proteins (RBPs) depending on the existence of classi-cal rna-binding domains. Both, rna-and RBP-centric methods have generated new knowledge of the rna-RBP interface and added an additional regulatory layer. In this review, we summarize recent advances in how RBP-lncrna interactions and various srnas shape cellular physiology and the development of liver diseases such as MAFLD and hepatocellular carcinoma.

关键词： hepatocellular carcinoma liver physiology NAFLD MAFLD noncoding rna rna-binding proteins

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noncoding rna as Therapeutic Targets for Hepatocellular Carcinoma

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SEMINARS IN LIVER DISEASE 2015年第1期35卷 63-74页

作者： George, Joseph Patel, Tushar Mayo Clin Dept Canc Biol Jacksonville FL 32224 USA Mayo Clin Dept Transplantat Jacksonville FL 32224 USA

Recent studies have suggested that noncoding rnas (ncrnas) contribute to the pathogenesis and progression of hepatocellular carcinoma (HCC). These rna genes may be involved in various pathobiological processes such as cell proliferation, apoptosis, angiogenesis, invasion, and metastasis. Aberrant expression of ncrna resulting from deregulated epigenetic, transcriptional, or posttranscriptional activity has been described in several studies. ncrnas are comprised of a highly diverse group of transcripts that include micrornas (mirnas) and long noncoding rnas (lncrnas) as well as several other types of rna genes. Understanding the molecular mechanisms by which ncrna contribute to hepatocarcinogenesis may enable the design of ncrna-based therapeutics for HCC. In this review, the authors provide a perspective on therapeutic applications based on the emerging evidence of a contributory role of mirnas and lncrnas to the pathogenesis and progression of HCC. In addition, ncrnas that are deregulated in expression in HCC may have utility as potential prognostic or diagnostic markers.

关键词： hepatocellular carcinoma noncoding rna microrna long noncoding rna biomarker

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noncoding rna for CR20, a cytokinin-repressed gene of cucumber

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PLANT MOLECULAR BIOLOGY 1996年第5期32卷 797-808页

作者： Teramoto, H Toyama, T Takeba, G Tsuji, H KYOTO UNIV FAC SCIDEPT BOTKYOTO 60601JAPAN KOBE WOMENS UNIV DEPT BIOLSUMA KUKOBE 654JAPAN

The CR20 gene was identified as a cytokinin-repressed gene in excised cotyledons of cucumber. We determined the sequences of some CR20 cDNAs with different structures and sequenced genomic clones for CR20. This gene consisted of three exons, and there were at least three types of transcript, which seemed to be generated by alternative splicing of the second intron. None of the CR20 transcripts included a long open reading frame (ORF). We isolated a cDNA of Arabidopsis thaliana with cucumber CR20 cDNA as a probe. This cDNA for a gene designated AtCR20-1 also lacked a long ORE A region of 180 nucleotides was conserved in the CR20 rna of cucumber and the AtCR20-1 rna of Arabidopsis, although the homology was relatively low when the entire sequences were compared. Each conserved region consisted of seven elements, and seems to form stable secondary structure. These suggest that CR20 rna may function as an rna that is not translated into a protein.

关键词： Arabidopsis Cucumis cytokinin noncoding rna

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The noncoding rna linc-ADAMTS5 cooperates with RREB1 to protect from intervertebral disc degeneration through inhibiting ADAMTS5 expression

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CLINICAL SCIENCE 2017年第10期131卷 965-979页

作者： Wang, Kun Song, Yu Liu, Wei Wu, Xinghuo Zhang, Yukun Li, Shuai Kang, Liang Tu, Ji Zhao, Kangcheng Hua, Wenbin Yang, Cao Huazhong Univ Sci & Technol Union Hosp Dept Orthoped Tongji Med Coll Wuhan Peoples R China First Hosp Wuhan Dept Orthoped Wuhan Peoples R China

Previous studies have indicated the important roles of ADAMTS5 in intervertebral disc degeneration (IDD). However, the mechanisms that regulate ADAMTS5 expression in nuclear pulposus (NP) cells remain largely unknown. Evidence suggests that intergenic transcription may be associated with genes that encode transcriptional regulators. Here, we identified a long intergenic noncoding rna, linc-ADAMTS5, which was transcribed in the opposite direction to ADAMTS5. In the present study, through mining computational algorithm programs, and publicly available data sets, we identified Ras-responsive element-binding protein 1 (RREB1) as a crucial transcription factor regulating the expression of ADAMTS5 in NP cells. rna pull-down, rna immunoprecipitation (RIP), in vitro binding assays, and gain and loss-of-function studies indicated that a physical interaction between linc-ADAMTS5 and splicing factor proline/glutamine-rich (SFPQ) facilitated the recruitment of RREB1 to binding sites within the ADAMTS5 promoter to induce chromatin remodeling. This resulted in subdued ADAMTS5 levels in cultured NP cells involving histone deacetylases (HDACs). In clinical NP tissues, linc-ADAMTS5 and RREB1 were correlated negatively with ADAMTS5 expression. Taken together, these results demonstrate that RREB1 cooperates with noncoding rna linc-ADAMTS5 to inhibit ADAMTS5 expression, thereby affecting degeneration of the extracellular matrix (ECM) of the intervertebral disc (IVD).

关键词： ADAMTS5 intervertebral disc degeneration noncoding rna

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noncoding rna-guided recruitment of transcription factors: A prevalent but undocumented mechanism?

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BIOESSAYS 2015年第9期37卷 936-941页

作者： Lee, Nara Steitz, Joan A. Yale Univ Sch Med Howard Hughes Med Inst Dept Mol Biophys & Biochem New Haven CT 06510 USA

High-fidelity binding of transcription factors (TFs) to DNA target sites is fundamental for proper regulation of cellular processes, as well as for the maintenance of cell identity. Recognition of cognate binding motifs in the genome is attributed by and large to the DNA binding domains of TFs. As an additional mode of conferring binding specificity, noncoding rnas (ncrnas) have been proposed to assist associated TFs in finding their binding sites by interacting with either DNA or rna in the vicinity of their target loci. However, a well-documented example of such a mechanism was lacking until we recently reported that a ncrna made by Epstein-Barr virus uses an rna-rna interaction with nascent transcripts generated from the viral genome to facilitate the recruitment of an interacting TF, PAX5, to viral DNA. This proof-of-principle finding suggests that cellular ncrnas may likewise function in guiding interacting TFs to chromatin target sites.

关键词： noncoding rna trans-acting ncrnas transcription factor binding transcription factor recruitment

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