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The double-edged sword of long non-coding rna: The role of human brain-specific BC200 rna in translational control, neurodegenerative diseases, and cancer

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MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH 2015年 766卷 58-67页

作者： Sosinska, Patrycja Mikula-Pietrasik, Justyna Ksiazek, Krzysztof Poznan Univ Med Sci Dept Pathophysiol PL-60806 Poznan Poland

The complexity of eukaryotic organisms involves the regulation of gene expression through DNA-protein, rna-DNA, rna-rna, and rna-protein interactions. The role of rna molecules in the regulation of genes in higher species has become even more evident with the discovery that about 97% of transcription products are represented by non-protein coding rnas (ncrnas) including short ncrnas and long ncrnas (Incrnas). In addition to the well-characterized role of ncrnas in different physiological cellular processes, numerous studies have also indicated the crucial roles of ncrnas in neurological diseases and cancer. Although involvement of short ncrna in those pathologies has already been well documented, there is only scarce evidence to show the participation of Incrnas. One of the examples of lncrnas is BC200 rna, which plays an important role in the regulation of dendritic protein expression. Mislocalization and overexpression of BC200 rna leads to inadequate rna delivery to the synapses and results in neurodegenerative processes of Alzheimer's disease and neoplastic changes in various groups of tissues. In this review, we summarize the current state of art in the field of the biological significance of Incrnas, with particular attention paid to the physiological and pathophysiological role of BC200 rna. (C) 2015 Elsevier B.V. All rights reserved.

关键词： BC200 rna Neurodegeneration non-coding rna

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A cautionary tale: the non-causal association between type 2 diabetes risk SNP, rs7756992, and levels of non-coding rna, CDKAL1-v1

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DIABETOLOGIA 2015年第4期58卷 745-748页

作者： Locke, Jonathan M. Wei, Fan-Yan Tomizawa, Kazuhito Weedon, Michael N. Harries, Lorna W. Univ Exeter Inst Biomed & Clin Sci Sch Med Exeter EX2 5DW Devon England Kumamoto Univ Dept Mol Physiol Fac Life Sci Kumamoto Japan

Intronic single nucleotide polymorphisms (SNPs) in the CDKAL1 gene are associated with risk of developing type 2 diabetes. A strong correlation between risk alleles and lower levels of the non-coding rna, CDKAL1-v1, has recently been reported in whole blood extracted from Japanese individuals. We sought to replicate this association in two independent cohorts: one using whole blood from white UK-resident individuals, and one using a collection of human pancreatic islets, a more relevant tissue type to study with respect to the aetiology of diabetes. Levels of CDKAL1-v1 were measured by real-time PCR using rna extracted from human whole blood (n = 70) and human pancreatic islets (n = 48). Expression with respect to genotype was then determined. In a simple linear regression model, expression of CDKAL1-v1 was associated with the lead type 2 diabetes-associated SNP, rs7756992, in whole blood and islets. However, these associations were abolished or substantially reduced in multiple regression models taking into account rs9366357 genotype: a moderately linked SNP explaining a much larger amount of the variation in CDKAL1-v1 levels, but not strongly associated with risk of type 2 diabetes. Contrary to previous findings, we provide evidence against a role for dysregulated expression of CDKAL1-v1 in mediating the association between intronic SNPs in CDKAL1 and susceptibility to type 2 diabetes. The results of this study illustrate how caution should be exercised when inferring causality from an association between disease-risk genotype and non-coding rna expression.

关键词： CDKAL1 Expression quantitative trait loci Genome-wide association studies non-coding rna Type 2 diabetes

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non-coding 7S rna inhibits transcription via mitochondrial rna polymerase dimerization

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CELL 2022年第13期185卷 2309-+页

作者： Zhu, Xuefeng Xie, Xie Das, Hrishikesh Tan, Benedict G. Shi, Yonghong Al-Behadili, Ali Peter, Bradley Motori, Elisa Valenzuela, Sebastian Posse, Viktor Gustafsson, Claes M. Haellberg, B. Martin Falkenberg, Maria Univ Gothenburg Dept Med Biochem & Cell Biol POB 440 S-40530 Gothenburg Sweden Karolinska Inst Dept Cell & Mol Biol S-17177 Stockholm Sweden Cologne Excellence Cluster Cellular Stress Respon D-50931 Cologne Germany Univ Cologne Inst Biochem Zulpicher Str 47 D-50674 Cologne Germany

The mitochondrial genome encodes 13 components of the oxidative phosphorylation system, and altered mitochondrial transcription drives various human pathologies. A polyadenylated, non-coding rna molecule known as 7S rna is transcribed from a region immediately downstream of the light strand promoter in mammalian cells, and its levels change rapidly in response to physiological conditions. Here, we report that 7S rna has a regulatory function, as it controls levels of mitochondrial transcription both in vitro and in cultured human cells. Using cryo-EM, we show that POLRMT dimerization is induced by interactions with 7S rna. The resulting POLRMT dimer interface sequesters domains necessary for promoter recognition and unwinding, thereby preventing transcription initiation. We propose that the non-coding 7S rna molecule is a component of a negative feedback loop that regulates mitochondrial transcription in mammalian cells.

关键词： mitochondria transcription POLRMT 7S rna SUV3 dimer cryo-EM mtDNA mtEXO non-coding rna

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Putting non-coding rna on Display with CRISPR

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MOLECULAR CELL 2015年第2期59卷 146-148页

作者： Perez-Pinera, Pablo Jones, Matthew F. Lal, Ashish Lu, Timothy K. Univ Illinois Dept Bioengn Urbana IL 61801 USA NCI Regulatory RNAs & Canc Sect Genet Branch Ctr Canc ResNIH Bethesda MD 20892 USA MIT Dept Elect Engn & Comp Sci Dept Biol Engn Elect Res Lab Cambridge MA 02139 USA

In a recent issue of Nature Methods, Shechner et al. (2015) reported the development of CRISPR Display (CRISP-Disp), which is a sophisticated, flexible, modular, and multiplexable platform for targeting different types of non-coding rnas (ncrnas) to genomic loci. CRISP-Disp will facilitate synthetic-biology applications and enable the elucidation of ncrna functions.

关键词： non-coding rna CRISPRS (Genetics) SYNTHETIC biology GENE targeting LOCUS (Genetics)

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A domain ontology for the non-coding rna field

A domain ontology for the non-coding RNA field

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IEEE International Conference on Bioinformatics and Biomedicine - Medical Informatics and Decision Making

作者： Huang, Jingshan Eilbeck, Karen Blake, Judith A. Dou, Dejing Natale, Darren A. Ruttenberg, Alan Smith, Barry Zimmermann, Michael T. Jiang, Guoqian Lin, Yu Wu, Bin He, Yongqun Zhang, Shaojie Wang, Xiaowei Zhang, He Liu, Zixing Tan, Ming Univ S Alabama Sch Comp South Biomed Informat Grp Mobile AL 36688 USA Univ Utah Sch Med Dept Biomed Informat Salt Lake City UT 84112 USA Jackson Lab Genome Informat Bar Harbor ME 04609 USA Univ Oregon CIS Dept Eugene OR 97403 USA Georgetown Univ Med Ctr Washington DC 20007 USA Univ Buffalo Buffalo NY 14214 USA Univ Buffalo Dept Philosophy Buffalo NY 14260 USA Mayo Clin Coll Med Rochester MN 55905 USA Univ Miami Miami FL 33146 USA Kunming Med Univ Affiliated Hosp 1 Kunming 650032 Yunnan Peoples R China Univ Michigan Ann Arbor MI 48109 USA Univ Cent Florida Orlando FL 32816 USA Washington Univ Sch Med St Louis MO 63108 USA Univ S Alabama Mobile AL 36688 USA Univ S Alabama MCI Mobile AL 36604 USA

ISBN: (纸本)9781467367981

Identification of non-coding rnas (ncrnas) has been significantly enhanced due to the rapid advancement in sequencing technologies. On the other hand, semantic annotation of ncrna data lag behind their identification, and there is a great need to effectively integrate discovery from relevant communities. To this end, the non-coding rna Ontology (NCRO) is being developed to provide a precisely defined ncrna controlled vocabulary, which can fill a specific and highly needed niche in unification of ncrna biology.

关键词： non-coding rna biological and biomedical ontologies domain ontology ontology development semantic data annotation and integration

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non-coding rnas as therapeutic targets in cancer and its clinical application

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Journal of Pharmaceutical Analysis 2024年第7期14卷 983-1010页

作者： Xuejiao Leng Mengyuan Zhang Yujing Xu Jingjing Wang Ning Ding Yancheng Yu Shanliang Sun Weichen Dai Xin Xue Nianguang Li Ye Yang Zhihao Shi National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine Nanjing University of Chinese MedicineNanjing210023China School of Medicine&Holistic Integrative Medicine Nanjing University of Chinese MedicineNanjing210023China Laboratory of Molecular Design and Drug Discovery School of ScienceChina Pharmaceutical UniversityNanjing211198China

Cancer genomics has led to the discovery of numerous oncogenes and tumor suppressor genes that play critical roles in cancer development and *** promote cell growth and proliferation,whereas tumor suppressor genes inhibit cell growth and *** dysregulation of these genes can lead to the development of *** studies have focused on non-coding rnas(ncrnas),including circular rna(circrna),long non-coding rna(lncrna),and microrna(mirna),as therapeutic targets for *** this article,we discuss the oncogenes and tumor suppressor genes of ncrnas associated with different types of cancer and their potential as therapeutic ***,we highlight the mechanisms of action of these genes and their clinical applications in cancer *** the molecular mechanisms underlying cancer development and identifying specific therapeutic targets are essential steps towards the development of effective cancer treatments.

关键词： non-coding rna Therapeutic targets Cancer Clinical application

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non-coding rnas to treat vascular smooth muscle cell dysfunction

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BRITISH JOUrnaL OF PHARMACOLOGY 2025年第2期182卷 246-280页

作者： Brown, Simon D. Klimi, Eftychia Bakker, Wilfried A. M. Beqqali, Abdelaziz Baker, Andrew H. Univ Edinburgh Queens Med Res Inst BHF Ctr Cardiovasc Sci 47 Little France Crescent Edinburgh EH16 4TJ Scotland Btavia Biosci BV Biosci Pk Leiden Leiden Netherlands Maastricht Univ Med Ctr Cardiovasc Res Inst Maastricht CARIM Maastricht Netherlands

Vascular smooth muscle cell (vSMC) dysfunction is a critical contributor to cardiovascular diseases, including atherosclerosis, restenosis and vein graft failure. Recent advances have unveiled a fascinating range of non-coding rnas (ncrnas) that play a pivotal role in regulating vSMC function. This review aims to provide an in-depth analysis of the mechanisms underlying vSMC dysfunction and the therapeutic potential of various ncrnas in mitigating this dysfunction, either preventing or reversing it. We explore the intricate interplay of micrornas, long-non-coding rnas and circular rnas, shedding light on their roles in regulating key signalling pathways associated with vSMC dysfunction. We also discuss the prospects and challenges associated with developing ncrna-based therapies for this prevalent type of cardiovascular pathology. image

关键词： atherosclerosis cardiovascular disease circular rna long non-coding rna microrna non-coding rna therapeutic oligonucleotides vascular smooth muscle cell

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non-coding rnas, a double-edged sword in breast cancer prognosis

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CANCER CELL INTErnaTIONAL 2025年第1期25卷 1-31页

作者： Solaimani, Maryam Hosseinzadeh, Sahar Abasi, Mozhgan Amol Univ Special Modern Technol Fac Biotechnol Amol Iran Mazandaran Univ Med Sci Fac Pharm & Med Biotechnol Sari Iran Mazandaran Univ Med Sci Fac Adv Technol Med Immunogenet Res Ctr Dept Tissue Engn & Appl Cell Sci POB 48175-861 Sari Iran

Cancer is a rising issue worldwide, and numerous studies have focused on understanding the underlying reasons for its occurrence and finding proper ways to defeat it. By applying technological advances, researchers are continuously uncovering and updating treatments in cancer therapy. Their vast functions in the regulation of cell growth and proliferation and their significant role in the progression of diseases, including cancer. This review provides a comprehensive analysis of ncrnas in breast cancer, focusing on long non-coding rnas such as HOTAIR, MALAT1, and NEAT1, as well as micrornas such as miR-21, miR-221/222, and miR-155. These ncrnas are pivotal in regulating cell proliferation, metastasis, drug resistance, and apoptosis. Additionally, we discuss experimental approaches that are useful for studying them and highlight the advantages and challenges of each method. We then explain the results of these clinical trials and offer insights for future studies by discussing major existing gaps. On the basis of an extensive number of studies, this review provides valuable insights into the potential of ncrnas in cancer therapy. Key findings show that even though the functions of ncrnas are vast and undeniable in cancer, there are still complications associated with their therapeutic use. Moreover, there is an absence of sufficient experiments regarding their application in mouse models, which is an area to work on. By emphasizing the crucial role of ncrnas, this review underscores the need for innovative approaches and further studies to explore their potential in cancer therapy.

关键词： Breast cancer-carcinoma Neoplasia non-coding rna Long non-coding rna Oncogene Tumor suppressor

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non-coding rnas Function in Periodontal Ligament Stem Cells

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STEM CELL REVIEWS AND REPORTS 2024年第6期20卷 1521-1531页

作者： Zhai, Wei Gao, Jie Qin, Wen Xu, Yuerong Fourth Mil Med Univ Natl Clin Res Ctr Oral Dis Shaanxi Clin Res Ctr Oral Dis Sch StomatolState Key Laboratory of Oral & Maxill Xian Peoples R China

non-coding rna has many types which has rich functions and plays an important role in the study of basic molecular mechanisms. Many non-coding rna have important implications for pluripotent stem cells and embryonic stem cells. It has been found to affect the self-renewal and osteogenesis of many types of stem cells. They have also been found to regulate stem cell proliferation and induct bone differentiation. Periodontal ligament stem cells are essential for the regeneration of periodontal tissue. In recent years, in the field of stomatology, studies have found that many non-coding rna also have significant regulatory effects on the proliferation and differentiation of periodontal stem cells and may become potential therapeutic targets for many common periodontal diseases such as periodontitis, bone/tooth/soft tissue loss and orthodontic treatment. Therefore, we summarized the current research status of non-coding rna in the field of molecular mechanism of periodontal ligament stem cells and prospected its future *** abstractBy Figdraw.

关键词： Periodontal Ligament stem Cells non-coding rna Periodontitis Orthodontics Mechanical Stress

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non-coding rnas as potential targets in metformin therapy for cancer

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CANCER CELL INTErnaTIONAL 2024年第1期24卷 333页

作者： Zhang, Yihan Wu, Yunhao Liu, Zixu Yang, Kangping Lin, Hui Xiong, Kai Nanchang Univ Affiliated Hosp 2 Jiangxi Med Coll Dept Gastroenterol Nanchang 330008 Jiangxi Peoples R China Jiangxi Med Coll Sch Clin Med 2 Nanchang Peoples R China Nanchang Univ Jiangxi Med Coll Sch Clin Med 1 Nanchang 330006 Jiangxi Peoples R China Sch Basic Med Sci Dept Pathophysiol Jiangxi Prov Key Lab Tumor Pathogenesis & Mol Path Nanchang Peoples R China

Metformin, a widely used oral hypoglycemic drug, has emerged as a potential therapeutic agent for cancer treatment. While initially known for its role in managing diabetes, accumulating evidence suggests that metformin exhibits anticancer properties through various mechanisms. Several cellular or animal experiments have attempted to elucidate the role of non-coding rna molecules, including micrornas and long non-coding rnas, in mediating the anticancer effects of metformin. The present review summarized the current understanding of the mechanisms by which non-coding rnas modulate the response to metformin in cancer cells. The regulatory roles of non-coding rnas, particularly mirnas, in key cellular processes such as cell proliferation, cell death, angiogenesis, metabolism and epigenetics, and how metformin affects these processes are discussed. This review also highlights the role of lncrnas in cancer types such as lung adenocarcinoma, breast cancer, and renal cancer, and points out the need for further exploration of the mechanisms by which metformin regulates lncrnas. In addition, the present review explores the potential advantages of metformin-based therapies over direct delivery of ncrnas, and this review highlights the mechanisms of non-coding rna regulation when metformin is combined with other therapies. Overall, the present review provides insights into the molecular mechanisms underlying the anticancer effects of metformin mediated by non-coding rnas, offering novel opportunities for the development of personalized treatment strategies in cancer patients.

关键词： Metformin non-coding rna Long non-coding rna Circular rna microrna Cancer

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