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noncoding rnas regulate alternative splicing in Cancer

JOUrnaL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 2021年第1期40卷 11-11页

作者： Liu, Yunze Liu, Xin Lin, Changwei Jia, Xianhong Zhu, Hongmei Song, Jun Zhang, Yi Xuzhou Med Univ Dept Gen Surg Affiliated Hosp Xuzhou 221000 Jiangsu Peoples R China Xuzhou Med Univ Dept Tradit Chinese Med Affiliated Hosp Xuzhou 221000 Jiangsu Peoples R China Xuzhou Med Univ Dept Endocrinol Affiliated Hosp Xuzhou 221000 Jiangsu Peoples R China Cent South Univ Dept Gastrointestinal Surg XiangYa Hosp 3 Changsha 410013 Peoples R China

AS (alternative splicing) is a fundamental process by which a gene can generate multiple distinct mrna transcripts to increase protein diversity. Defects in AS influence the occurrence and development of many diseases, including cancers, and are frequently found to participate in various aspects of cancer biology, such as promoting invasion, metastasis, apoptosis resistance and drug resistance. Ncrnas (noncoding rnas) are an abundant class of rnas that do not encode proteins. Ncrnas include mirnas (micrornas), lncrnas (long noncoding rnas), circrnas (circular rnas) and snrnas (small nuclear rnas) and have been proven to act as regulatory molecules that mediate cancer processes through AS. Ncrnas can directly or indirectly influence a plethora of molecular targets to regulate cis-acting elements, trans-acting factors, or pre-mrna transcription at multiple levels, affecting the AS process and generating alternatively spliced isoforms. Consequently, ncrna-mediated AS outcomes affect multiple cellular signaling pathways that promote or suppress cancer progression. In this review, we summarize the current mechanisms by which ncrnas regulate AS in cancers and discuss their potential clinical applications as biomarkers and therapeutic targets.

关键词： Alternative splicing Cancer noncoding rna mirna lncrna circrna snrna

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noncoding rnas from tissue-derived small extracellular vesicles: Roles in diabetes and diabetic complications

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MOLECULAR METABOLISM 2022年 58卷 101453-101453页

作者： Chang, Wenguang Li, Mengyang Song, Lin Miao, Suo Yu, Wanpeng Wang, Jianxun Qingdao Univ Affiliated Hosp Inst Translat Med Qingdao Peoples R China Qingdao Univ Coll Med Sch Basic Med Sci Qingdao Peoples R China Qingdao Univ Coll Med Qingdao Peoples R China

Diabetes is a systemic disease, and its progression involves multiple organ dysfunction. However, the exact mechanisms underlying pathological progression remain unclear. Small extracellular vesicles (sEVs) mediate physiological and pathological signaling communication between organs and have been shown to have important regulatory roles in diabetes and its complications in recent years. In particular, the majority of studies in the diabetes-related research field have focused on the noncoding rnas carried by sEVs. Researchers found that noncoding rna sorting into sEVs is not random but selective. Both tissue origin differences and environmental variations affect the cargo of sEVs. In addition, the function of sEVs differs according to the tissue they derive from;for example, sEVs derived from adipose tissue regulate insulin sensitivity in the periphery, while sEVs derived from bone marrow promote 13-cell regeneration. Therefore, understanding the roles of sEVs from different tissues is important for elucidating their molecular mechanisms and is necessary for the application of sEVs as therapeutic agents for diabetes treatment in the future. In this review, we summarized current studies on the mechanisms of noncoding rna sorting into sEVs, as well as the research progress on the effects of sEVs from different tissue origins and noncoding rnas in diabetes and diabetic complications. The knowledge of noncoding rnas in sEVs will help us better understand the role of sEVs in the diabetes progression.(c) 2022 The Author(s). Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://***/licenses/by-nc-nd/4.0/).

关键词： Extracellular vesicles Diabetes noncoding rna Exosomes

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noncoding rnas: new insights into the odontogenic differentiation of dental tissue-derived mesenchymal stem cells

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STEM CELL RESEARCH & THERAPY 2019年第1期10卷 297-297页

作者： Fang, Fuchun Zhang, Kaiying Chen, Zhao Wu, Buling Southern Med Univ Nanfang Hosp Dept Stomatol 1838 Guangzhou Ave North Guangzhou 510515 Guangdong Peoples R China Southern Med Univ Coll Stomatol 1838 GuangZhou Ave North Guangzhou 510515 Guangdong Peoples R China

Odontoblasts are cells that contribute to the formation of the dental pulp complex. The differentiation of dental tissue-derived mesenchymal stem cells into odontoblasts comprises many factors and signaling pathways. noncoding rnas (ncrnas), comprising a substantial part of poly-A tail mature rnas, are considered transcriptional noise. Emerging evidence has shown that ncrnas have key functions in the differentiation of mesenchymal stem cells. In this review, we discussed two major types of ncrnas, including micrornas (mirnas) and long noncoding rnas (lncrnas), in terms of their role in the odontogenic differentiation of dental tissue-derived stem cells. Recent findings have demonstrated important functions for mirnas and lncrnas in odontogenic differentiation. It is expected that ncrnas will become promising therapeutic targets for dentin regeneration based on stem cells.

关键词： Dental tissue Mesenchymal stem cells Long noncoding rna Microrna noncoding rna Odontogenic differentiation

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noncoding rnas in oral cancer

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WILEY INTERDISCIPLINARY REVIEWS-rna 2023年第3期14卷 e1754-e1754页

作者： Balakittnen, Jaikrishna Weeramange, Chameera Ekanayake Wallace, Daniel F. Duijf, Pascal H. G. Cristino, Alexandre S. Kenny, Liz Vasani, Sarju Punyadeera, Chamindie Queensland Univ Technol Fac Hlth Ctr Biomed Technol Sch Biomed Sci Kelvin Grove Qld Australia Griffith Univ Griffith Inst Drug Discovery Sal & Liquid Biopsy Translat Lab Nathan Qld Australia Univ Jaffna Fac Allied Hlth Sci Dept Med Lab Sci Jaffna Sri Lanka Queensland Univ Technol Fac Hlth Ctr Genom & Personalised Hlth Sch Biomed Sci Brisbane Qld Australia Queensland Univ Technol Fac Hlth Translat Res Inst Sch Biomed Sci Woolloongabba Qld Australia Queensland Univ Queensland Ctr Data Sci Technol Brisbane Qld Australia Univ Oslo Fac Med Inst Clin Med Oslo Norway Oslo Univ Hosp Dept Med Genet Oslo Norway Univ Queensland Diamantina Inst Brisbane Qld Australia Griffith Univ Griffith Inst Drug Discovery Nathan Qld Australia Royal Brisbane & Womens Hosp Canc Care Serv Herston Qld Australia Univ Queensland Fac Med Brisbane Qld Australia Royal Brisbane & Womens Hosp Dept Otolaryngol Herston Qld Australia Griffith Univ Menzies Hlth Inst Gold Coast Qld Australia

Oral cancer (OC) is the most prevalent subtype of cancer arising in the head and neck region. OC risk is mainly attributed to behavioral risk factors such as exposure to tobacco and excessive alcohol consumption, and a lesser extent to viral infections such as human papillomaviruses and Epstein-Barr viruses. In addition to these acquired risk factors, heritable genetic factors have shown to be associated with OC risk. Despite the high incidence, biomarkers for OC diagnosis are lacking and consequently, patients are often diagnosed in advanced stages. This delay in diagnosis is reflected by poor overall outcomes of OC patients, where 5-year overall survival is around 50%. Among the biomarkers proposed for cancer detection, noncoding rna (ncrna) can be considered as one of the most promising categories of biomarkers due to their role in virtually all cellular processes. Similar to other cancer types, changes in expressions of ncrnas have been reported in OC and a number of ncrnas have diagnostic, prognostic, and therapeutic potential. Moreover, some ncrnas are capable of regulating gene expression by various mechanisms. Therefore, elucidating the current literature on the four main types of ncrnas namely, microrna, lncrna, snorna, piwi-rna, and circular rna in the context of OC pathogenesis is timely and would enable further improvements and innovations in diagnosis, prognosis, and treatment of OC. This article is categorized under: rna in Disease and Development > rna in Disease rna in Disease and Development > rna in Development

关键词： diagnosis noncoding rna oral cancer prognosis therapeutics

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noncoding rnas in cataract formation: Star molecules emerge in an endless stream

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PHARMACOLOGICAL RESEARCH 2022年第0期184卷 106417页

作者： Chen, Silong Zhang, Chengshou Shen, Lifang Hu, Jianghua Chen, Xiangjun Yu, Yibo Zhejiang Univ Affiliated Hosp 2 Ctr Eye Coll Med 88 Jiefang Rd Hangzhou Peoples R China Zhejiang Univ Sch Med Affiliated Hosp 2 Dept OphthalmolJiande Branch Hangzhou Peoples R China Zhejiang Univ Inst Translat Med Sch Med 268 Kaixuan Rd Hangzhou Peoples R China

For decades, research on the pathological mechanism of cataracts has usually focused on the abnormal protein changes caused by a series of risk factors. However, an entire class of molecules, termed non-coding rna (ncrna), was discovered in recent years and proven to be heavily involved in cataract formation. Recent studies have recognized the key regulatory roles of ncrnas in cataracts by shaping cellular activities such as proliferation, apoptosis, migration and epithelial-mesenchymal transition (EMT). This review summarizes our current insight into the biogenesis, properties and functions of ncrnas and then discusses the development of research on ncrnas in cataracts. Considering the significant role of ncrna in cataract formation, research on novel associated regulatory mechanisms is urgently needed, and the development of therapeutic alternatives for the treatment of cataracts seems promising.

关键词： noncoding rna Circular rna Microrna Long noncoding rna Cataract Ophthalmology

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noncoding rnas in cancer ferroptosis: From biology to clinical opportunity

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BIOMEDICINE & PHARMACOTHERAPY 2023年第1期165卷 115053-115053页

作者： Shan, Chan Liang, Yan Wang, Kun Li, Peifeng Qingdao Univ Affiliated Hosp Inst Translat Med Coll Med Qingdao 266021 Peoples R China Qingdao Univ Sch Pharm Dept Pharmaceut Qingdao 266021 Peoples R China

Ferroptosis is a recently discovered pattern of programmed cell death that is nonapoptotic and irondependent. It is involved in lipid peroxidation dependent on reactive oxygen species. Ferroptosis has been verified to play a crucial regulatory role in a variety of pathological courses of disease, in particularly cancer. Emerging research has highlighted the potential of ferroptosis in tumorigenesis, cancer development and resistance to chemotherapy. However, the regulatory mechanism of ferroptosis remains unclear, which limits the application of ferroptosis in cancer treatment. noncoding rnas (ncrnas) are noncoding transcripts that regulate gene expression in various ways to affect the malignant phenotypes of cancer cells. At present, the biological function and underlying regulatory mechanism of ncrnas in cancer ferroptosis have been partially elucidated. Herein, we summarize the current knowledge of the central regulatory network of ferroptosis, with a focus on the regulatory functions of ncrnas in cancer ferroptosis. The clinical application and prospects of ferroptosis-related ncrnas in cancer diagnosis, prognosis and anticancer therapies are also discussed. Elucidating the function and mechanism of ncrnas in ferroptosis, along with assessing the clinical significance of ferroptosis-related ncrnas, provides new perspectives for understanding cancer biology and treatment approaches, which may benefit numerous cancer patients in the future.

关键词： Ferroptosis noncoding rna Cell death Regulatory mechanism Cancer therapy

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noncoding rnas: New regulatory code in chondrocyte apoptosis and autophagy

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WILEY INTERDISCIPLINARY REVIEWS-rna 2020年第4期11卷 e1584-e1584页

作者： Jiang, Siyu Liu, Yi Xu, Billian Zhang, Yan Yang, Min Guangdong Med Univ Marine Med Res Inst Guangdong Zhanjiang Guangdong Key Lab Res & Dev Nat Drugs Zhanjiang 524023 Peoples R China Guangdong Med Univ Dept Pharmacol Zhanjiang 524023 Guangdong Peoples R China Tianjin Binhai New Area Tanggu Obstet & Gynecol H Operating Room Tianjin Peoples R China Shenzhen Ritzcon Biol Technol Co LTD Shenzhen Peoples R China

Osteoarthritis (OA) is a bone and joint disease characterized by progressive cartilage degradation. In the face of global trends of population aging, OA is expected to become the fourth most common disabling disease by 2020. Nevertheless, the detailed pathogenesis of OA has not yet been elucidated. noncoding rnas (ncrnas), including long noncoding rnas, micrornas, and circular rnas, do not encode proteins but have recently emerged as important regulators of apoptosis and autophagy of chondrocytes, thereby highlighting a potential role in chondrocyte injury leading to OA onset and progression. We here review recent findings on these regulatory roles of ncrnas to provide new directions for research on the pathogenesis of OA and offer new therapeutic targets for prevention and treatment. This article is categorized under: rna in Disease and Development > rna in Disease rna in Disease and Development > rna in Development

关键词： apoptosis autophagy chondrocytes noncoding rna osteoarthritis

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noncoding rnas improve the predictive power of network medicine

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2023年第45期120卷 e2301342120-e2301342120页

作者： Gysi, Deisy Morselli Barabasi, Albert-Laszlo Univ Fed Parana Dept Stat BR-81531990 Curitiba Brazil Northeastern Univ Network Sci Inst Boston MA 02115 USA Northeastern Univ Dept Phys Boston MA 02115 USA Harvard Med Sch Brigham & Womens Hosp Dept Med Channing Div Network Med Boston MA 02115 USA US Dept Vet Affairs Boston MA 02130 USA Cent European Univ Dept Network & Data Sci H-1051 Budapest Hungary

Network medicine has improved the mechanistic understanding of disease, offering quantitative insights into disease mechanisms, comorbidities, and novel diagnostic tools and therapeutic treatments. Yet, most network-based approaches rely on a comprehensive map of protein-protein interactions (PPI), ignoring interactions mediated by noncoding rnas (ncrnas). Here, we systematically combine experimentally confirmed binding interactions mediated by ncrna with PPI, constructing a comprehensive network of all physical interactions in the human cell. We find that the inclusion of ncrna expands the number of genes in the interactome by 46% and the number of interactions by 107%, significantly enhancing our ability to identify disease modules. Indeed, we find that 132 diseases lacked a statistically significant disease module in the protein-based interactome but have a statistically significant disease module after inclusion of ncrna- mediated interactions, making these diseases accessible to the tools of network medicine. We show that the inclusion of ncrnas helps unveil disease-disease relationships that were not detectable before and expands our ability to predict comorbidity patterns between diseases. Taken together, we find that including noncoding interactions improves both the breath and the predictive accuracy of network medicine.

关键词： noncoding rna network medicine network science mirna ncrna

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noncoding rnas in Alzheimer's disease

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WILEY INTERDISCIPLINARY REVIEWS-rna 2018年第2期9卷 e1463页

作者： Idda, M. Laura Munk, Rachel Abdelmohsen, Kotb Gorospe, Myriam NIA Lab Genet & Genom Intramural Res Program NIH 251 Bayview Blvd Baltimore MD 21224 USA

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the main cause of dementia among the elderly worldwide. Despite intense efforts to develop drugs for preventing and treating AD, no effective therapies are available as yet, posing a growing burden at the personal, medical, and socioeconomic levels. AD is characterized by the production and aggregation of amyloid beta (A beta) peptides derived from amyloid precursor protein (APP), the presence of hyperphosphorylated microtubule-associated protein Tau (MAPT), and chronic inflammation leading to neuronal loss. A beta accumulation and hyperphosphorylated Tau are responsible for the main histopathological features of AD, A beta plaques, and neurofibrillary tangles (NFTs), respectively. However, the full spectrum of molecular factors that contribute to AD pathogenesis is not known. noncoding (nc)rnas, including micrornas (mirnas), long noncoding rnas (lncrnas), and circular rnas (circrnas), regulate gene expression at the transcriptional and posttranscriptional levels in various diseases, serving as biomarkers and potential therapeutic targets. There is rising recognition that ncrnas have been implicated in both the onset and pathogenesis of AD. Here, we review the ncrnas implicated posttranscriptionally in the main AD pathways and discuss the growing interest in targeting regulatory ncrnas therapeutically to combat AD pathology. This article is categorized under: rna in Disease and Development > rna in Disease

关键词： amyloid plaques circrna lncrna mirna neurodegeneration neurofibrillary tangles noncoding rna posttranscriptional gene regulation

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Nerna: A negative data generation framework for machine learning applications of noncoding rnas

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COMPUTERS IN BIOLOGY AND MEDICINE 2023年第1期159卷 106861-106861页

作者： Orhan, Mehmet Emin Demirci, Yilmaz Mehmet Demirci, Mueserref Duygu Sacar Abdullah Gul Univ Grad Sch Engn & Sci Dept Bioengn Kayseri Turkiye Abdullah Gul Univ Fac Engn Dept Engn Sci Kayseri Turkiye Abdullah Gul Univ Fac Life & Nat Sci Dept Bioengn Kayseri Turkiye

Many supervised machine learning based noncoding rna (ncrna) analysis methods have been developed to classify and identify novel sequences. During such analysis, the positive learning datasets usually consist of known examples of ncrnas and some of them might even have weak or strong experimental validation. On the contrary, there are neither databases listing the confirmed negative sequences for a specific ncrna class nor standardized methodologies developed to generate high quality negative examples. To overcome this challenge, a novel negative data generation method, Nerna (negative rna), is developed in this work. Nerna uses known examples of given ncrna sequences and their calculated structures for octal representation to create negative sequences in a manner similar to frameshift mutations but without deletion or insertion. Nerna is tested individually with four different ncrna datasets including microrna (mirna), transfer rna (trna), long noncoding rna (lncrna), and circular rna (circrna). Furthermore, a species-specific case analysis is per-formed to demonstrate and compare the performance of Nerna for mirna prediction. The results of 1000 fold cross-validation on Decision Tree, Naive Bayes and Random Forest classifiers, and deep learning algorithms such as Multilayer Perceptron, Convolutional Neural Network, and Simple feedforward Neural Networks indicate that models obtained by using Nerna generated datasets, achieves substantially high prediction performance. Nerna is released as an easy-to-use, updatable and modifiable KNIME workflow that can be downloaded with example datasets and required extensions. In particular, Nerna is designed to be a powerful tool for rna sequence data analysis.

关键词： rna noncoding rna Data generation Machine learning

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