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      Bioinformatics analysis of the circRNA–miRNA–mRNA network for non-small cell lung cancer

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          Abstract

          Objective

          Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancers, but its pathogenesis has not been fully elucidated. Therefore, it is valuable to explore the pathogenesis of NSCLC to improve diagnosis and identify novel treatment biomarkers.

          Methods

          Circular (circ)RNA, micro (mi)RNA, and gene expression datasets of NSCLC were analyzed to identify those that were differentially expressed between tumor and healthy tissues. Common genes were found and pathway enrichment analyses were performed. Survival analysis was used to identify hub genes, and their level of methylation and association with immune cell infiltration were analyzed. Finally, an NSCLC circRNA–miRNA–mRNA network was constructed.

          Results

          Eight miRNAs and 211 common genes were identified. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that cell projection morphogenesis, blood vessel morphogenesis, muscle cell proliferation, and synapse organization were enriched. Ten hub genes were found, of which the expression of DTL and RRM2 was significantly related to NSCLC patient prognosis. Significant methylation changes and immune cell infiltration correlations with DTL and RRM2 were also detected.

          Conclusions

          hsa_circ_0001947/hsa-miR-637/RRM2 and hsa_circ_0072305/hsa-miR-127-5p/DTL networks were constructed, and identified molecules may be involved in the occurrence and development of NSCLC.

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          Most cited references20

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          miRWalk: An online resource for prediction of microRNA binding sites

          miRWalk is an open-source platform providing an intuitive interface that generates predicted and validated miRNA-binding sites of known genes of human, mouse, rat, dog and cow. The core of miRWalk is the miRNA target site prediction with the random-forest-based approach software TarPmiR searching the complete transcript sequence including the 5’-UTR, CDS and 3’-UTR. Moreover, it integrates results other databases with predicted and validated miRNA-target interactions. The focus is set on a modular design and extensibility as well as a fast update cycle. The database is available using Python, MySQL and HTML/Javascript Database URL: http://mirwalk.umm.uni-heidelberg.de.
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            MicroRNA in lung cancer: role, mechanisms, pathways and therapeutic relevance

            Lung cancer is the cardinal cause of cancer-related deaths with restricted recourse of therapy throughout the world. Clinical success of therapies is not very promising due to - late diagnosis, limited therapeutic tools, relapse and the development of drug resistance. Recently, small ∼20-24 nucleotides molecules called microRNAs (miRNAs) have come into the limelight as they play outstanding role in the process of tumorigenesis by regulating cell cycle, metastasis, angiogenesis, metabolism and apoptosis. miRNAs essentially regulate gene expression via post-transcriptional regulation of mRNA. Nevertheless, few studies have conceded the role of miRNAs in activation of gene expression. A large body of data generated by numerous studies is suggestive of their tumor-suppressing, oncogenic, diagnostic and prognostic biomarker roles in lung cancer. They have also been implicated in regulating cancer cell metabolism and resistance or sensitivity towards chemotherapy and radiotherapy. Further, miRNAs have also been convoluted in regulation of immune checkpoints - Programmed death 1 (PD-1) and its ligand (PD-L1). These molecules play a significant role in tumor immune escape leading to the generation of a microenvironment favouring tumor growth and progression. Therefore, it is imperative to explore the expression of miRNA and understand its relevance in lung cancer and development of anti-cancer strategies (anti - miRs, miR mimics and micro RNA sponges). In view of the above, the role of miRNA in lung cancer has been dissected and the associated mechanisms and pathways are discussed in this review.
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              DiseaseMeth version 2.0: a major expansion and update of the human disease methylation database

              The human disease methylation database (DiseaseMeth, http://bioinfo.hrbmu.edu.cn/diseasemeth/) is an interactive database that aims to present the most complete collection and annotation of aberrant DNA methylation in human diseases, especially various cancers. Recently, the high-throughput microarray and sequencing technologies have promoted the production of methylome data that contain comprehensive knowledge of human diseases. In this DiseaseMeth update, we have increased the number of samples from 3610 to 32 701, the number of diseases from 72 to 88 and the disease–gene associations from 216 201 to 679 602. DiseaseMeth version 2.0 provides an expanded comprehensive list of disease–gene associations based on manual curation from experimental studies and computational identification from high-throughput methylome data. Besides the data expansion, we also updated the search engine and visualization tools. In particular, we enhanced the differential analysis tools, which now enable online automated identification of DNA methylation abnormalities in human disease in a case-control or disease–disease manner. To facilitate further mining of the disease methylome, three new web tools were developed for cluster analysis, functional annotation and survival analysis. DiseaseMeth version 2.0 should be a useful resource platform for further understanding the molecular mechanisms of human diseases.
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                Author and article information

                Journal
                J Int Med Res
                J. Int. Med. Res
                IMR
                spimr
                The Journal of International Medical Research
                SAGE Publications (Sage UK: London, England )
                0300-0605
                1473-2300
                12 June 2020
                June 2020
                : 48
                : 6
                : 0300060520929167
                Affiliations
                [1 ]Department of Respiratory Medicine, Zhongshan Hospital, Xiamen University, Xiamen City, Fujian Province, China
                [2 ]Department of Basic Medicine, College of Life Sciences, Sichuan University, Chengdu, China
                [3 ]Department of Internal Medicine and Oncology, Zhongshan Hospital, Xiamen University, Xiamen City, Fujian Province, China
                Author notes

                *These authors contributed equally to this work.

                #These authors contributed equally to this work.

                [*]Weixin Wu, Department of Internal Medicine and Oncology, Zhongshan Hospital, Xiamen University, 209 Hubin South Road, Siming District, Xiamen City, Fujian Province, 361000, China. Email: wu3170536@ 123456sina.com
                Author information
                https://orcid.org/0000-0003-3062-6787
                Article
                10.1177_0300060520929167
                10.1177/0300060520929167
                7294496
                32527185
                59a1cdbb-2967-4b53-80d7-1e2ca035c59a
                © The Author(s) 2020

                Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 17 January 2020
                : 1 May 2020
                Categories
                Pre-Clinical Research Report
                Custom metadata
                corrected-proof
                ts2

                non-small cell lung cancer,bioinformatics,hub gene,circular rna,microrna,differential expression,methylation,survival analysis

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