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      CircEIF4G2 Promotes Tumorigenesis and Progression of Osteosarcoma by Sponging miR-218

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          Abstract

          Circular RNAs (circRNAs) play a key role in regulating the tumorigenesis and development of human cancers, including osteosarcoma (OS). Of note, the molecular mechanism underlying the progression of OS has remained largely unclear. The present study identified that a novel circRNA circEIF4G2 was upregulated in OS tissues and cells. Moreover, we constructed a circEIF4G2-mediated ceRNA network and revealed that circEIF4G2 was involved in regulating multiple cancer pathways, such as the EGFR signaling pathway, the PI3K-Akt signaling pathway, and the ErbB signaling pathway. Loss-of-function assays showed that circEIF4G2 knockdown significantly suppressed OS cell proliferation, migration, and invasion. Mechanically, we found that circEIF4G2 could directly bind to miR-218, and miR-218 mediated the effect of circEIF4G2 knockdown on OS progression. In conclusion, the present study showed that circEIF4G2 could be a potential biomarker for OS.

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          The novel roles of circRNAs in human cancer

          Covalently closed single-stranded circular RNAs (circRNAs) consist of introns or exons and are widely present in eukaryotic cells. CircRNAs generally have low expression levels and relatively stable structures compared with messenger RNAs (mRNAs), most of which are located in the cytoplasm and often act in cell type and tissue-specific manners, indicating that they may serve as novel biomarkers. In recent years, circRNAs have gradually become a hotspot in the field of RNA and cancer research, but the functions of most circRNAs have not yet been discovered. Known circRNAs can affect the biogenesis of cancers in diverse ways, such as functioning as a microRNA (miRNA) sponges, combining with RNA binding proteins (RBPs), working as a transcription factor and translation of proteins. In this review, we summarize the characteristics and types of circRNAs, introduce the biogenesis of circRNAs, discuss the emerging functions and databases on circRNAs and present the current challenges of circRNAs studies.
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            Circular RNAs (circRNAs) in cancer

            Circular RNAs (circRNAs) are a class of non-coding RNAs that do not have 5' end caps or 3' end poly (A) tails. There are more than one hundred thousand genes that encode circRNAs. Clinical data show that there are differences in the expression of circRNAs in a variety of diseases, including cancer, suggesting that circRNA has a regulatory effect on some diseases. Further studies reveal that circRNA can be used as an endogenous competitive RNA, thereby regulating the proliferation, invasion or other physiological activities of tumor cells. In addition, some circRNAs located in the nucleus can regulate the transcription of the parental gene by binding to RNA polymerase II. circRNA can also combine with proteins to influence the cell cycle. Furthermore, recent studies have shown that circRNA can encode proteins, similarly to mRNA. circRNAs are found extensively in human cells and have tissue specificity. They have the potential to be used in clinical applications as tumor markers and therapeutic targets.
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              The translation factor eIF-4E promotes tumor formation and cooperates with c-Myc in lymphomagenesis.

              The mammalian target of rapamycin, mTOR, regulates cell growth and proliferation. Here we show that the initiation factor of translation (eIF-4E), a downstream effector of mTOR, has oncogenic effects in vivo and cooperates with c-Myc in B-cell lymphomagenesis. We found that c-Myc overrides eIF-4E-induced cellular senescence, whereas eIF-4E antagonizes c-Myc-dependent apoptosis in vivo. Our results implicate activation of eIF-4E as a key event in oncogenic transformation by phosphoinositide-3 kinase and Akt.
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                Author and article information

                Contributors
                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2020
                23 May 2020
                : 2020
                : 8386936
                Affiliations
                1Spinal Surgery Department, Shenzhen People's Hospital, Shenzhen, Guangdong 518000, China
                2Orthopedics Department, The Eight Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong 518000, China
                Author notes

                Guest Editor: Tao Huang

                Author information
                https://orcid.org/0000-0003-4152-4495
                https://orcid.org/0000-0001-5493-8967
                Article
                10.1155/2020/8386936
                7273497
                33457419
                757fd583-8d45-48ba-a493-1047c723a9dc
                Copyright © 2020 Erhu Lin et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 1 February 2020
                : 30 March 2020
                Categories
                Research Article

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