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non-coding rna and drug resistance in head and neck cancer

Cancer Drug Resistance 2024年第1期7卷 419-438页

作者： Yulong Zhang Yingming Peng Bingqin Lin Shuai Yang Feiqiang Deng Xuan Yang An Li Wanyi Xia Chenxi Gao Shaona Lei Wei Liao Qi Zeng Cancer Center The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000GuangdongChina Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Infectious Diseases Traditional Chinese Medicine Bureau of Guangdong Provincethe Fifth Affiliated HospitalSun Yat-sen UniversityZhuhai 519000GuangdongChina Department of Radiotherapy and Minimally Invasive Surgery Cancer CenterThe Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000GuangdongChina Department of Otolaryngology and Head and Neck Surgery The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000GuangdongChina

Head and neck cancer(HNC)is ranked as the sixth most common malignant tumor,and the overall survival rate with current treatment options remains concerning,primarily due to drug resistance that develops following antitumor *** studies indicate that non-coding rnas play a crucial role in drug resistance among HNC *** article systematically reviews the current research landscape,explores novel targets and treatment strategies related to non-coding rnas and HNC resistance,raises some unresolved issues,and discusses five promising research directions in this field:ferroptosis,nanomedicine,exosomes,proteolysis-targeting chimeras(PROTACs),and artificial *** hope that our work will contribute to advancing research on overcoming HNC resistance through the regulation of non-coding rnas.

关键词： Head and neck cancer non-coding rna microrna long non-coding rna circular rna drug resistance

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Prediction of small non-coding rna in bacterial genomes using support vector machines

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EXPERT SYSTEMS WITH APPLICATIONS 2010年第8期37卷 5549-5557页

作者： Chang, Tzu-Hao Wu, Li-Ching Lin, Jun-Hong Huang, Hsien-Da Liu, Baw-Jhiune Cheng, Kuang-Fu Horng, Jorng-Tzong Natl Cent Univ Dept Comp Sci & Informat Engn Chungli Taiwan Natl Cent Univ Inst Syst Biol & Bioinformat Chungli Taiwan Natl Chiao Tung Univ Inst Bioinformat Dept Biol Sci & Technol Hsinchu Taiwan Yuan Ze Univ Dept Comp Sci & Informat Engn Chungli Taiwan China Med Univ Grad Inst Stat Shenyang Peoples R China China Med Univ Dept Publ Hlth Shenyang Peoples R China China Med Univ Ctr Biostat Shenyang Peoples R China Asia Univ Dept Bioinformat Taichung Taiwan

Small non-coding rna genes have been shown to play important regulatory roles in a variety of cellular processes, but prediction of non-coding rna genes is a great challenge, using either an experimental or a computational approach, due to the characteristics of srnas, which are that srnas are small in size, are not translated into proteins and show variable stability. Most known srnas have been identified in Escherichia coli and have been shown to be conserved in closely related organisms. We have developed an integrative approach that searches highly conserved intergenic regions among related bacterial genomes for combinations of characteristics that have been extracted from known E. coli srna genes. Support vector machines (SVM) were then used with these characteristics to predict novel srna genes. (c) 2010 Elsevier Ltd. All rights reserved.

关键词： Expert systems Support vector machines Machine learning Bioinformatics non-coding rna

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non-coding rna therapeutics in cardiovascular diseases and risk factors: Systematic review

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non-coding rna RESEARCH 2023年第4期8卷 487-506页

作者： Ardiana, Meity Fadila, Asiyah Nurul Zuhra, Zakirah Kusuma, Nabilla Merdika Rurus, Made Edgard Surya Erlangga Oceandy, Delvac Dr Soetomo Gen Hosp Dept Cardiol & Vasc Med Surabaya Indonesia Airlangga Univ Fac Med Surabaya Indonesia Univ Indonesia Fac Med Jakarta Indonesia Hang Tuah Univ Fac Med Surabaya Indonesia Univ Manchester Fac Biol Med & Hlth Div Cardiovasc Sci Manchester England

At present, rna-based therapy which includes therapies using non-coding rnas (ncrnas), antisense oligonucleotides (ASOs), and aptamers are gaining widespread attention as possible ways to target genes in various cardiovascular diseases (CVDs), thereby serving as a promising therapeutic approach for CVDs and risk factors management. However, data are primarily in an early stage. A systematic review was carried out using literature from several databases (Pubmed, Cochrane, Scopus, and DOAJR) following the PRISMA guidelines. Of the 64 articles reviewed, 39 papers were included in this review with three main types of rnas: aptamers, antisense oligonucleotides (ASOs), and small-interfering rna (sirna). All studies were human clinical trials. rna-based therapies were demonstrated to be efficacious in treating various CVDs and controlling cardiovascular risk factors. They are generally safe and well-tolerated. However, data are still in the early stage and warrant further investigation.

关键词： non-coding rna rna therapeutics Cardiovascular diseases Cardiovascular risk factors Cardiogenetics

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ncPro-ML: An integrated computational tool for identifying non-coding rna promoters in multiple species

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COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOUrnaL 2020年 18卷 2445-2452页

作者： Tang, Qiang Nie, Fulei Kang, Juanjuan Chen, Wei Chengdu Univ Tradit Chinese Med Innovat Inst Chinese Med & Pharm Chengdu 611137 Peoples R China North China Univ Sci & Technol Ctr Genom & Computat Biol Scholl Life Sci Tangshan 063210 Peoples R China Southern Med Univ Affiliated Foshan Matern & Child Healthcare Hosp Foshan Matern & Child Healthcare Hosp Foshan 528000 Peoples R China North China Univ Sci & Technol Sch Publ Hlth Tangshan 063210 Peoples R China

The promoter is located near the transcription start sites and regulates transcription initiation of the gene. Accurate identification of promoters is essential for understanding the mechanism of gene regulation. Since experimental methods are costly and ineffective, developing efficient and accurate computational tools to identify promoters are necessary. Although a series of methods have been proposed for identifying promoters, none of them is able to identify the promoters of non-coding rna (ncrna). In the present work, a new method called ncPro-ML was proposed to identify the promoter of ncrna in Homo sapiens and Mus musculus, in which different kinds of sequence encoding schemes were used to convert DNA sequences into feature vectors. To test the length effect, for each species, datasets including sequences with different lengths were built. The results demonstrated that ncPro-ML achieved the best performance based on the dataset with the sequence length of 221 nucleotides for human and mouse. The performances of ncPro-ML were also satisfying from both independent dataset test and cross-species test. The results indicate that the proposed predictor can server as a powerful tool for the discovery of ncrna promoters. In addition, a web-server for ncPro-ML was developed, which can be freely accessed at http://***/ncPro-ML/. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.

关键词： non-coding rna Promoter Sequence length effect Ensemble learning

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Activation of p53 by MEG3 non-coding rna

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JOUrnaL OF BIOLOGICAL CHEMISTRY 2007年第34期282卷 24731-24742页

作者： Zhou, Yunli Zhong, Ying Wang, Yingying Zhang, Xun Batista, Dalia L. Gejman, Roger Ansell, Peter J. Zhao, Jing Weng, Catherine Klibanski, Anne Massachusetts Gen Hosp Neuendrocrine Unit Boston MA 02114 USA Harvard Univ Sch Med Boston MA 02114 USA Massachusetts Gen Hosp Neuropathol Unit Boston MA 02114 USA

MEG3 is a maternally expressed imprinted gene suggested to function as a non-coding rna. Our previous studies suggest that MEG3 has a function of tumor suppression. The tumor suppressor p53 plays a central role in tumor suppression and mediates the functions of many other tumor suppressors. Therefore, we hypothesized that MEG3 functions through activation of p53. We found that transfection of expression constructs for MEG3 and its isoforms results in a significant increase in p53 protein levels and dramatically stimulates p53-dependent transcription from a p53-responsive promoter. Using this as the functional assay, we demonstrated that the open reading frames encoded by MEG3 transcripts are not required for MEG3 function, and the folding of MEG3 rna is critical to its function, supporting the concept that MEG3 functions as a non-coding rna. We further found that MEG3 stimulates expression of the growth differentiation factor 15 (GDF15) by enhancing p53 binding to the GDF15 gene promoter. Interestingly, MEG3 does not stimulate p21(CIP1) expression, suggesting that MEG3 can regulate the specificity of p53 transcriptional activation. p53 degradation is mainly mediated by the mouse double minute 2 homolog (MDM2). We found that MDM2 levels were down-regulated in cells transfected with MEG3, suggesting that MDM2 suppression contributes at least in part to p53 accumulation induced by MEG3. Finally, we found that MEG3 is able to inhibit cell proliferation in the absence of p53. These data suggest that MEG3 non-coding rna may function as a tumor suppressor, whose action is mediated by both p53-dependent and p53-independent pathways.

关键词： non-coding rna ENZYME activation ANTIONCOGENES CELL proliferation TUMORS -- Growth

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Mechanism of Down-regulation of rna Polymerase III-transcribed non-coding rna Genes in Macrophages by Leishmania

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JOUrnaL OF BIOLOGICAL CHEMISTRY 2011年第8期286卷 6614-6626页

作者： Rana, Tanu Misra, Smita Mittal, Mukul K. Farrow, Anitra L. Wilson, Keith T. Linton, MacRae F. Fazio, Sergio Willis, Ian M. Chaudhuri, Gautam Meharry Med Coll Dept Microbiol & Immunol Nashville TN 37208 USA Vanderbilt Univ Div Gastroenterol Nashville TN 37232 USA Vanderbilt Univ Div Cardiovasc Med Nashville TN 37232 USA Vet Affairs Tennessee Valley Healthcare Syst Nashville TN 37212 USA Albert Einstein Coll Med Dept Biochem Bronx NY 10461 USA Albert Einstein Coll Med Dept Syst & Computat Biol Bronx NY 10461 USA

The parasitic protozoan Leishmania invades mammalian macrophages to establish infection. We reported previously that Leishmania manipulates the expression of several non-coding rna genes (e. g. Alu rna, B1 rna, and signal recognition particle rna) in macrophages to favor the establishment of their infection in the phagolysosomes of these cells (Ueda, Y., and Chaudhuri, G. (2000) J. Biol. Chem. 275, 19428-19432;Misra, S., Tripathi, M. K., and Chaudhuri, G. (2005) J. Biol. Chem. 280, 29364-29373). We report here the mechanism of this down-regulation. We found that the non-coding rna (ncrna) genes that are repressed by Leishmania infection in macrophages contain a "B-box" in their promoters and thus require the polymerase III transcription factor TFIIIC for their expression. We also found that Leishmania promastigotes through their surface protease (leishmanolysin or gp63) activate the thrombin receptor PAR1 in the macrophages. This activation of PAR1 raised the cytosolic concentration of Ca2+ into the micromolar range, thereby activating the Ca2+-dependent protease mu-calpain. mu-Calpain then degraded TFIIIC110 to inhibit the expression of the selected ncrna genes. Avirulent stocks of Leishmania not expressing surface gp63 failed to down-regulate ncrnas in the exposed macrophages. Inhibition of PAR1 or calpain 1 in macrophages made them resistant to Leishmania infection. These data suggest that macrophage PAR1 and calpain 1 are potential drug targets against leishmaniasis.

关键词： rna polymerases non-coding rna MACROPHAGES RESEARCH LEISHMANIA PROTEOLYTIC enzymes THROMBIN DRUG targeting

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Fexrna: Exploratory Data Analysis and Feature Selection of non-coding rna

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IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS 2021年第6期18卷 2795-2801页

作者： Amin, Noorul McGrath, Annette Chen, Yi-Ping Phoebe La Trobe Univ Dept Comp Sci & Informat Technol Melbourne Vic 3086 Australia CSIRO Data61 Brisbane Qld 4001 Australia

non-coding rna (ncrna) is involved in many biological processes and diseases in all species. Many ncrna datasets exist that provide ncrna data in FASTA format which is well suited for biomedical purposes. However, for ncrna analysis and classification, statistical learning methods require hidden numerical features from the data. Furthermore, in the literature, a wealth of sequence intrinsic features has been proposed for ncrna identification. The extraction of hidden features, their analysis, and usage of a suitable set of features is crucial for the performance of any statistical learning method. To alleviate the posed challenges, we generated 96 feature datasets from ncrna widely used features. The feature datasets are based on rnaCentral and consist of species, ncrna types, and expert databases that are available on the Fexrna platform. Additionally, the feature datasets are explored and analysed to provide statistical information, univariate, and bivariate analysis. We sought to determine which of these 17 features would be most appropriate to use in developing ncrna classification approaches. For feature selection (FS), a two-phase hierarchical FS framework based on correlation and majority voting is proposed and evaluated on 5 species. The Fexrna platform provides information about ncrna feature analysis and selection.

关键词： Feature extraction rna Proteins Encoding Statistical learning Databases Peptides non-coding rna feature selection feature extraction data exploration

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BcMF11, a putative pollen-specific non-coding rna from Brassica campestris ssp chinensis

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JOUrnaL OF PLANT PHYSIOLOGY 2007年第8期164卷 1097-1100页

作者： Song, Jiang-Hua Cao, Jia-Shu Yu, Xiao-Lin Xiang, Xun Zhejiang Univ Inst Sci Vegetales Lab Cell & Mol Biol Hangzhou 310029 Peoples R China

A full-length cDNA, BcMF11, has been cloned from Chinese cabbage (Brassica campestris L. ssp. chinensis Makino) using rapid amplification of the cDNA ends (RACE) based on a pollen-specific cDNA fragment (DN237921). The BcMF11 cDNA has a total length of 828 bp with poly (A) tail. Analysis of the sequence demonstrated that BcMF11 is a novel non-coding rna which has no prominent open reading frame (ORF) or coding capacity. No significant similarities were observed between BcMF11 and previously published sequences in GenBank. Transcription analysis indicated that BcMF11 is a novel pollen-specific ncrna and may be involved in the pollen development of Chinese cabbage. (C) 2006 Elsevier GmbH. All rights reserved.

关键词： Brassica campestris ssp chinensis expression patterns molecular cloning non-coding rna pollen development

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Long non-coding rna ZFAS1 Regulates Fibrosis and Scortosis in the Cell Model of Diabetic Nephropathy Through miR-525-5p/SGK1 Axis

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APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY 2024年第7期196卷 3731-3746页

作者： Zhuang, Langen Jin, Guoxi Wang, Qiong Ge, Xiaoxu Pei, Xiaoyan Bengbu Med Coll Dept Endocrinol Dept Oncol Gynecol Affiliated Hosp 1 287 Changhuai Rd Bengbu 233004 Anhui Peoples R China Jiaotong Univ Dept Pathol Dept Endocrinol Tongren Hosp 1111Xianxia Rd Shanghai 200336 Peoples R China

Diabetic nephropathy (DN) is a common clinical syndrome in diabetic patients. Functional characterization of non-coding (ncrnas) involved in the progression of DN can provide insights into the diagnosis and therapeutic management of DN. Human kidney proximal tubular epithelial cells (HK-2) were challenged by high glucose (HG, 50 mM) as a cell model of DN. The expression level of long non-coding rna (lncrna) ZFAS1 was quantified by qRT-PCR. The proteins and cytokines related to fibrosis and scortosis in DN (NLRP3, GSDMD-N, IL-1 beta and Caspase 1, fibronectin, collagen I, collagen III, IL-1 beta, and IL-18) were examined by western blot or ELISA. rna precipitation and luciferase reporter activity experiments were conducted to assess the molecular associations. ZFAS1 and SGK1 were highly induced in HK-2 cells challenged with HG, while miR-525-5p downregulated upon HG treatment. ZFAS1 knockdown attenuated HG-induced fibrosis and scortosis in HK-2 cells by reducing the levels of NLRP3, GSDMD-N, Caspase 1, fibronectin, collagen I/III, IL-1 beta, and IL-18. Mechanically, ZFAS1 knockdown protected HK-2 cells from HG-induced injury by upregulating miR-525-5p and repressing SGK1 expression. Overall, our results suggest that knocking down ZFAS1 may be formulated as a protective strategy in ameliorating DN progression through regulating miR-525-5p/SGK1 pathway. Targeting ZFAS1 could be further explored as a potential approach for the management of DN.

关键词： Diabetic nephropathy non-coding rna ZFAS1 miR-525-5p SGK1

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rna-directed DNA methylation requires stepwise binding of silencing factors to long non-coding rna

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PLANT JOUrnaL 2014年第2期79卷 181-191页

作者： Boehmdorfer, Gudrun Rowley, M. Jordan Kucinski, Jan Zhu, Yongyou Amies, Ivan Wierzbicki, Andrzej T. Univ Michigan Dept Mol Cellular & Dev Biol Ann Arbor MI 48109 USA

Ribonucleic acid-mediated transcriptional gene silencing (known as rna-directed DNA methylation, or RdDM, in Arabidopsis thaliana) is important for influencing gene expression and the inhibition of transposons by the deposition of repressive chromatin marks such as histone modifications and DNA methylation. A key event in de novo methylation of DNA by RdDM is the production of long non-coding rna (lncrna) by rna polymerase V (Pol V). Little is known about the events that connect Pol V transcription to the establishment of repressive chromatin modifications. Using rna immunoprecipitation, we elucidated the order of events downstream of lncrna production and discovered interdependency between lncrna-associated proteins. We found that the effector protein ARGONAUTE4 (AGO4) binds lncrna independent of the rna-binding protein INVOLVED IN DE NOVO2 (IDN2). In contrast, IDN2 binds lncrna in an AGO4-dependent manner. We further found that the de novo DNA methyltransferase DOMAINS REARRANGED METHYL-TRANSFERASE2 (DRM2) also associates with lncrna produced by Pol V and that this event depends on AGO4 and IDN2. We propose a model where the silencing proteins AGO4, IDN2 and DRM2 bind to lncrna in a stepwise manner, resulting in DNA methylation of RdDM target loci.

关键词： non-coding rna DNA methyltransferase Argonaute INVOLVED IN DE NOVO2 Arabidopsis thaliana

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