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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      Circular RNA PVT1 promotes the invasion and epithelial–mesenchymal transition of breast cancer cells through serving as a competing endogenous RNA for miR-204-5p

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          Abstract

          Purpose

          Circular RNAs (circRNAs) are a class of covalently closed circular RNA transcripts and have been found to regulate the progression of human malignancies. The objective of this study was to identify the functions of circRNAs in breast cancer (BCa).

          Patients and methods

          BCa and adjacent non-cancerous tissues were collected from 99 patients. Kaplan–Meier analysis was used to analyze the relationship between circPVT1 and prognosis. CircPVT1 expression levels in BCa tissues and cell lines were detected via PCR. Transfection technology was used to silence circPVT1 and overexpress miR-204-5p. Cell biological behavior was analyzed, and epithelial-mesenchymal transition (EMT) related proteins were detected by Western blot. In vivo experiments were performed with the subcutaneous xenograft tumor model.

          Results

          CircPVT1 was markedly overexpressed in BCa tissues and cell lines. Higher expression of circPVT1 was correlated with poor prognosis of BCa patients. Knockdown circPVT1 significantly suppressed the proliferation, migration and invasion of BCa cells invitro, and suppressed BCa tumor growth invivo. CircPVT1 knockdown upregulated E-cadherin and downregulated N-cadherin, Vimentin, Slug and Twist in BCa cells. Moreover, circPVT1 could serve as a competing endogenous RNA (ceRNA) for miR-204-5p, and restoration of miR-204-5p abrogated the oncogenic role of circPVT1 in BCa cells.

          Conclusion

          CircPVT1 as a potentially valuable biomarker for BCa diagnosis and therapeutic target for BCa treatment. CircPVT1 might promote the invasion and EMT of BCa cells by serving as aceRNA for miR-204-5p.

          Most cited references10

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          Epithelial-mesenchymal transitions in development and disease.

          The epithelial to mesenchymal transition (EMT) plays crucial roles in the formation of the body plan and in the differentiation of multiple tissues and organs. EMT also contributes to tissue repair, but it can adversely cause organ fibrosis and promote carcinoma progression through a variety of mechanisms. EMT endows cells with migratory and invasive properties, induces stem cell properties, prevents apoptosis and senescence, and contributes to immunosuppression. Thus, the mesenchymal state is associated with the capacity of cells to migrate to distant organs and maintain stemness, allowing their subsequent differentiation into multiple cell types during development and the initiation of metastasis.
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            The oncogenic role of circPVT1 in head and neck squamous cell carcinoma is mediated through the mutant p53/YAP/TEAD transcription-competent complex

            Background Circular RNAs are a class of endogenous RNAs with various functions in eukaryotic cells. Worthy of note, circular RNAs play a critical role in cancer. Currently, nothing is known about their role in head and neck squamous cell carcinoma (HNSCC). The identification of circular RNAs in HNSCC might become useful for diagnostic and therapeutic strategies in HNSCC. Results Using samples from 115 HNSCC patients, we find that circPVT1 is over-expressed in tumors compared to matched non-tumoral tissues, with particular enrichment in patients with TP53 mutations. circPVT1 up- and down-regulation determine, respectively, an increase and a reduction of the malignant phenotype in HNSCC cell lines. We show that circPVT1 expression is transcriptionally enhanced by the mut-p53/YAP/TEAD complex. circPVT1 acts as an oncogene modulating the expression of miR-497-5p and genes involved in the control of cell proliferation. Conclusions This study shows the oncogenic role of circPVT1 in HNSCC, extending current knowledge about the role of circular RNAs in cancer. Electronic supplementary material The online version of this article (doi:10.1186/s13059-017-1368-y) contains supplementary material, which is available to authorized users.
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              The Emerging Function and Mechanism of ceRNAs in Cancer.

              Complex diseases, such as cancer, are often associated with aberrant gene expression at both the transcriptional and post-transcriptional level. Over the past several years, competing endogenous RNAs (ceRNAs) have emerged as an important class of post-transcriptional regulators that alter gene expression through a miRNA-mediated mechanism. Recent studies in both solid tumors and hematopoietic malignancies showed that ceRNAs have significant roles in cancer pathogenesis by altering the expression of key tumorigenic or tumor-suppressive genes. Characterizing the identity, function, and mechanism of the ceRNAs will not only further our fundamental understanding of RNA-mediated cancer pathogenesis, but may also shed light on the development of new RNA-based therapeutic strategies for treating cancer.

                Author and article information

                Journal
                Onco Targets Ther
                Onco Targets Ther
                OTT
                ott
                OncoTargets and therapy
                Dove
                1178-6930
                31 December 2019
                2019
                : 12
                : 11817-11826
                Affiliations
                [1 ]First Department of Oncology, Cangzhou Central Hospital of Hebei Province , Cangzhou 061001, People’s Republic of China
                Author notes
                Correspondence: Qingzhao Bian First Department of Oncology, Cangzhou Central Hospital of Hebei Province , 16 Xinhua West Road, Yunhe District, Cangzhou, Hebei Province061001, People’s Republic of China Email bqz01782@163.com
                Article
                180850
                10.2147/OTT.S180850
                7502987
                32982273
                6d85bed7-b854-4c10-9994-18324746dbcd
                © 2020 Bian.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 19 July 2018
                : 26 April 2019
                Page count
                Figures: 7, Tables: 1, References: 21, Pages: 10
                Categories
                Original Research

                Oncology & Radiotherapy
                breast cancer,circular rna pvt1,prognosis,epithelial-mesenchymal transition,competing endogenous rna,microrna-204-5p

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