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      Regulating COX10-AS1 / miR-142-5p / PAICS axis inhibits the proliferation of non-small cell lung cancer

      research-article
      a , a , b , c , d , e , #
      Bioengineered
      Taylor & Francis
      Non-small cell lung cancer (NSCLC), COX10-AS1, MIR-142-5P, PAICS, glycolysis

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          ABSTRACT

          Non-small cell lung cancer (NSCLC) is one of the main causes of death in the world. To improve the diagnostic level and find new biological targets,GSE datasets were selected from GEO databaseto analyze the differential expression genes and construct ceRNA network. Cell apoptosis detection showed that both the early and late apoptosis rates were increased after inhibition of COX10-AS1. Glycolysis cell-based assay also found that the content of L-lactate decreased significantly after using miR-142-5p mimics but increased after using si-COX10-AS1. Dual-luciferase reporter analysis showed that the luciferase activity of PAICS-WT reporter vector was inhibited by miR-142-5p mimics, but there was no significant change in PAICS-MUT reporter vector after transfection of miR-142-5p mimics. And overexpression of miR-142-5p reduced the level of PAICS, but inhibition of miR-142-5p expression increased the expression of PAICS. After using COX10-AS1, the expression of PAICS inhibited by miR-142-5p was restored. Through bioinformatics analysis, we constructed the COX10-AS1/miR-142-5p/PAICS axis, which is a ceRNA regulatory network. We confirmed that COX10-AS1 down-expression can restore the inhibitory effect of miR-142-5p on PAICS, promote the apoptosis of NSCLC cells, and inhibit the proliferation of NSCLC cells. This process may be mediated by the activation of glycolysis pathway. The glycolysis-related gene PAICS may be a new and significant target for the regulation of the development of NSCLC.

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          Most cited references40

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          Understanding the Warburg effect: the metabolic requirements of cell proliferation.

          In contrast to normal differentiated cells, which rely primarily on mitochondrial oxidative phosphorylation to generate the energy needed for cellular processes, most cancer cells instead rely on aerobic glycolysis, a phenomenon termed "the Warburg effect." Aerobic glycolysis is an inefficient way to generate adenosine 5'-triphosphate (ATP), however, and the advantage it confers to cancer cells has been unclear. Here we propose that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass (e.g., nucleotides, amino acids, and lipids) needed to produce a new cell. Supporting this idea are recent studies showing that (i) several signaling pathways implicated in cell proliferation also regulate metabolic pathways that incorporate nutrients into biomass; and that (ii) certain cancer-associated mutations enable cancer cells to acquire and metabolize nutrients in a manner conducive to proliferation rather than efficient ATP production. A better understanding of the mechanistic links between cellular metabolism and growth control may ultimately lead to better treatments for human cancer.
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            The biology and management of non-small cell lung cancer.

            Important advancements in the treatment of non-small cell lung cancer (NSCLC) have been achieved over the past two decades, increasing our understanding of the disease biology and mechanisms of tumour progression, and advancing early detection and multimodal care. The use of small molecule tyrosine kinase inhibitors and immunotherapy has led to unprecedented survival benefits in selected patients. However, the overall cure and survival rates for NSCLC remain low, particularly in metastatic disease. Therefore, continued research into new drugs and combination therapies is required to expand the clinical benefit to a broader patient population and to improve outcomes in NSCLC.
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              miRBase: annotating high confidence microRNAs using deep sequencing data

              We describe an update of the miRBase database (http://www.mirbase.org/), the primary microRNA sequence repository. The latest miRBase release (v20, June 2013) contains 24 521 microRNA loci from 206 species, processed to produce 30 424 mature microRNA products. The rate of deposition of novel microRNAs and the number of researchers involved in their discovery continue to increase, driven largely by small RNA deep sequencing experiments. In the face of these increases, and a range of microRNA annotation methods and criteria, maintaining the quality of the microRNA sequence data set is a significant challenge. Here, we describe recent developments of the miRBase database to address this issue. In particular, we describe the collation and use of deep sequencing data sets to assign levels of confidence to miRBase entries. We now provide a high confidence subset of miRBase entries, based on the pattern of mapped reads. The high confidence microRNA data set is available alongside the complete microRNA collection at http://www.mirbase.org/. We also describe embedding microRNA-specific Wikipedia pages on the miRBase website to encourage the microRNA community to contribute and share textual and functional information.
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                Author and article information

                Journal
                Bioengineered
                Bioengineered
                Bioengineered
                Taylor & Francis
                2165-5979
                2165-5987
                29 July 2021
                2021
                29 July 2021
                : 12
                : 1
                : 4643-4653
                Affiliations
                [a ]Department of Oncology, Ruijin Hospital Wuxi Branch, Shanghai Jiao Tong University School of Medicine; , Wuxi, China
                [b ]Department of oncology, The People's Hospital of Rugao; , Jiangsu, Rugao, China
                [c ]Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine; , Zhejiang, China
                [d ]Department of Clinical medicine, Yangzhou University’s Medical Faculty; , Jiangsu, China
                [e ]Department of Oncology, The Affiliated Changzhou No.2 People's Hospital with Nanjing Medical University; , Jiangsu, Changzhou, China
                Author notes
                CONTACT Wenyu Zhu townxinyu@ 123456sina.com Department of Oncology,The Affiliated Changzhou No.2 People’s Hospital with Nanjing Medical University; , 213002, China
                [#]

                These authors contribute equally.

                Article
                1957072
                10.1080/21655979.2021.1957072
                8806450
                34323174
                542e0482-4ad5-4ec3-9e1e-9b26235b543b
                © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Page count
                Figures: 6, Tables: 3, References: 40, Pages: 11
                Categories
                Research Article
                Research Paper

                Biomedical engineering
                non-small cell lung cancer (nsclc),cox10-as1,mir-142-5p,paics,glycolysis
                Biomedical engineering
                non-small cell lung cancer (nsclc), cox10-as1, mir-142-5p, paics, glycolysis

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