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      Circular RNAs function as ceRNAs to regulate and control human cancer progression

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          Abstract

          Circular RNAs (circRNAs) are connected at the 3′ and 5′ ends by exon or intron cyclization, forming a complete ring structure. circRNA is more stable and conservative than linear RNA and abounds in various organisms. In recent years, increasing numbers of reports have found that circRNA plays a major role in the biological functions of a network of competing endogenous RNA (ceRNA). circRNAs can compete together with microRNAs (miRNAs) to influence the stability of target RNAs or their translation, thus, regulating gene expression at the transcriptional level. circRNAs are involved in biological processes such as tumor cell proliferation, apoptosis, invasion, and migration as ceRNAs. circRNAs, therefore, represent promising candidates for clinical diagnosis and treatment. Here, we review the progress in studying the role of circRNAs as ceRNAs in tumors and highlight the participation of circRNAs in signal transduction pathways to regulate cellular functions.

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          Most cited references41

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          The JAK2/STAT3 signaling pathway is required for growth of CD44⁺CD24⁻ stem cell-like breast cancer cells in human tumors.

          Intratumor heterogeneity is a major clinical problem because tumor cell subtypes display variable sensitivity to therapeutics and may play different roles in progression. We previously characterized 2 cell populations in human breast tumors with distinct properties: CD44+CD24- cells that have stem cell-like characteristics, and CD44-CD24+ cells that resemble more differentiated breast cancer cells. Here we identified 15 genes required for cell growth or proliferation in CD44+CD24- human breast cancer cells in a large-scale loss-of-function screen and found that inhibition of several of these (IL6, PTGIS, HAS1, CXCL3, and PFKFB3) reduced Stat3 activation. We found that the IL-6/JAK2/Stat3 pathway was preferentially active in CD44+CD24- breast cancer cells compared with other tumor cell types, and inhibition of JAK2 decreased their number and blocked growth of xenografts. Our results highlight the differences between distinct breast cancer cell types and identify targets such as JAK2 and Stat3 that may lead to more specific and effective breast cancer therapies.
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            Coordinated circRNA Biogenesis and Function with NF90/NF110 in Viral Infection

            Circular RNAs (circRNAs) generated via back-splicing are enhanced by flanking complementary sequences. Expression levels of circRNAs vary under different conditions, suggesting participation of protein factors in their biogenesis. Using genome-wide siRNA screening that targets all human unique genes and an efficient circRNA expression reporter, we identify double-stranded RNA-binding domain containing immune factors NF90/NF110 as key regulators in circRNA biogenesis. NF90/NF110 promote circRNA production in the nucleus by associating with intronic RNA pairs juxtaposing the circRNA-forming exon(s); they also interact with mature circRNAs in the cytoplasm. Upon viral infection, circRNA expression is decreased, in part owing to the nuclear export of NF90/NF110 to the cytoplasm. Meanwhile, NF90/NF110 released from circRNP complexes bind to viral mRNAs as part of their functions in antiviral immune response. Our results therefore implicate a coordinated regulation of circRNA biogenesis and function by NF90/NF110 in viral infection.
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              Converging roles of caspases in inflammasome activation, cell death and innate immunity.

              Inflammatory and apoptotic caspases are central players in inflammation and apoptosis, respectively. However, recent studies have revealed that these caspases have functions beyond their established roles. In addition to mediating cleavage of the inflammasome-associated cytokines interleukin-1β (IL-1β) and IL-18, inflammatory caspases modulate distinct forms of programmed cell death and coordinate cell-autonomous immunity and other fundamental cellular processes. Certain apoptotic caspases assemble structurally diverse and dynamic complexes that direct inflammasome and interferon responses to fine-tune inflammation. In this Review, we discuss the expanding and interconnected roles of caspases that highlight new aspects of this family of cysteine proteases in innate immunity.
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                Author and article information

                Contributors
                zengzhaoyang@csu.edu.cn
                xiongwei@csu.edu.cn
                Journal
                Mol Cancer
                Mol. Cancer
                Molecular Cancer
                BioMed Central (London )
                1476-4598
                7 April 2018
                7 April 2018
                2018
                : 17
                : 79
                Affiliations
                [1 ]ISNI 0000 0004 1757 7615, GRID grid.452223.0, The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, , Xiangya Hospital, Central South University, ; Changsha, Hunan China
                [2 ]ISNI 0000 0001 0379 7164, GRID grid.216417.7, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, , Basic Medical Science School and Cancer Research Institute, Central South University, ; Changsha, Hunan China
                [3 ]GRID grid.431010.7, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, , The Third Xiangya Hospital, Central South University, ; Changsha, Hunan China
                [4 ]ISNI 0000 0001 0675 4725, GRID grid.239578.2, Department of Cancer Biology, , Lerner Research Institute, Cleveland Clinic, ; Cleveland, OH USA
                Article
                827
                10.1186/s12943-018-0827-8
                5889847
                29626935
                9724ad8b-705a-4e2a-bd90-00a7d50c1e1b
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 5 December 2017
                : 26 March 2018
                Categories
                Review
                Custom metadata
                © The Author(s) 2018

                Oncology & Radiotherapy
                circular rnas,cerna,cancer,gene expression regulation
                Oncology & Radiotherapy
                circular rnas, cerna, cancer, gene expression regulation

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