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      Potential Role of circPVT1 as a proliferative factor and treatment target in esophageal carcinoma

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          Abstract

          Background

          Many circRNAs have been reported to play important roles in cancer development and have the potential to serve as a novel class of biomarkers for clinical diagnosis. However, the role of circRNAs in esophageal carcinoma (EC) remains unclear. In the current study, we investigated the potential role of circPVT1 in esophageal carcinoma.

          Methods

          Quantitative real-time PCR was performed to detect circPVT1 levels. CircPVT1-specific siRNA or plasmids were used to knock down or overexpression the target RNA. Hoechst Staining was implemented to evaluate the ratio of cell apoptosis. Transwell migration assays were carried out to study the effects of circPVT1 on esophageal squamous cell carcinoma cell invasion. RegRNA 2.0 was used for bioinformatics analysis. The expression levels of Pax-4, Pax-6, PPARα and PPAR-γ were assessed using Western blot.

          Results

          In the present study, we demonstrated a significant up-regulation of circPVT1 levels in EC tissues and cancer cell lines. The levels of circPVT1 decreased significantly when the cells were maintained to over-confluence. These results suggested a potential role for circPVT1 in cell proliferation. In addition, overexpressing circPVT1 in TE-10 cell promoted invasive ability of cancer cell. In contrast, siRNA knockdown of circPVT1 inhibited this phenomenon, leading to increased apoptosis levels of TE-10 cell. What’s more, miR-4663 had the effect of inhibiting tumor growth by downregulated Paxs and upregulated PPARs. Whereas, after the addition of circPVT1, this effect no longer worked, suggesting that circPVT1 may affect the malignancy of the tumor by affecting miRNA and regulating the levels of Paxs and PPARs.

          Conclusions

          Collectively, our study reveals a critical role for circPVT1 in esophageal carcinoma, which may provide new insights of this circRNA as a biomarker for the diagnosis and treatment target of EC.

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          Most cited references29

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          The circRNA circAGFG1 acts as a sponge of miR-195-5p to promote triple-negative breast cancer progression through regulating CCNE1 expression

          Background In recent years, circular RNAs (circRNAs), a new star of non-coding RNA, have been emerged as vital regulators and gained much attention for involvement of initiation and progression of diverse kinds of human diseases, especially cancer. However, regulatory role, clinical significance and underlying mechanisms of circRNAs in triple-negative breast cancer (TNBC) still remain largely unknown. Methods Here, the expression profile of circRNAs in 4 pairs of TNBC tissues and adjacent non-tumor tissues was analyzed by RNA-sequencing. Quantitative real-time PCR and in situ hybridization were used to determine the level and prognostic values of circAGFG1 in two TNBC cohorts. Then, functional experiments in vitro and in vivo were performed to investigate the effects of circAGFG1 on tumor growth and metastasis in TNBC. Mechanistically, fluorescent in situ hybridization, dual luciferase reporter assay, RNA pull-down and RNA immunoprecipitation experiments were performed to confirm the interaction between circAGFG1 and miR-195-5p in TNBC. Results We found that circAGFG1 was evidently up-regulated in TNBC, and its level was correlated with clinical stage, pathological grade and poor prognosis of patients with TNBC. The results indicated that circAGFG1 could promote TNBC cell proliferation, mobility and invasion as well as tumorigenesis and metastasis in vivo. Mechanistic analysis showed that circAGFG1 may act as a ceRNA (competing endogenous RNA) of miR-195-5p to relieve the repressive effect of miR-195-5p on its target cyclin E1 (CCNE1). Conclusions Our findings suggest that circAGFG1 promotes TNBC progression through circAGFG1/miR-195-5p/CCNE1 axis and it may serve as a new diagnostic marker or target for treatment of TNBC patients. Electronic supplementary material The online version of this article (10.1186/s12943-018-0933-7) contains supplementary material, which is available to authorized users.
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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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              CircRNA hsa_circRNA_101996 increases cervical cancer proliferation and invasion through activating TPX2 expression by restraining miR‐8075

              In recent years, circular RNAs have been shown to serve as essential regulators in several human cancers. Nevertheless, the function and mechanism of CircRNA in cervical cancer remain elusive. In the present study, we showed that hsa_circRNA_101996 was highly expressed in cervical cancer tissues compared with matched normal tissues by bioinformatics analysis. We showed that the expression level of hsa_circRNA_101996 in cervical cancer tissues was positively correlated with TNM stage, tumor size, and lymph node metastasis. Moreover, higher levels of hsa_circRNA_101996 were related to poor outcomes of cervical cancer patients. We found that knockdown of hsa_circRNA_101996 significantly inhibited the proliferation, cell cycle, migration, and invasion of cervical cancer cells. Mechanistically, we demonstrated that hsa_circRNA_101996 served as a sponge of miR-8075, which targeted TPX2 in cervical cancer cells. We showed that miR-8075 that was downregulated in cervical cancer tissues repressed cervical cancer cell proliferation, migration, and invasion. Furthermore, we validated that upregulation of TPX2 by hsa_circRNA_101996-mediated inhibition of miR-8075 contributed to cervical cancer proliferation, migration, and invasion. Taken together, our findings revealed a novel mechanism that hsa_circRNA_101996-miR-8075-TPX2 network promoted cervical cancer progression.
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                Author and article information

                Contributors
                zhongrr1985@126.com
                zhuozhichen@tju.edu.cn
                xiaomilan163@163.com
                moziink@163.com
                +86 60363581 , zhptjgh@163.com
                Journal
                Cancer Cell Int
                Cancer Cell Int
                Cancer Cell International
                BioMed Central (London )
                1475-2867
                15 October 2019
                15 October 2019
                2019
                : 19
                : 267
                Affiliations
                [1 ]ISNI 0000 0004 1757 9434, GRID grid.412645.0, Department of Geriatrics, , Tianjin Medical University General Hospital, ; Tianjin, 300052 People’s Republic of China
                [2 ]Tianjin Geriatrics Institute, Tianjin, 300052 People’s Republic of China
                [3 ]ISNI 0000 0004 1761 2484, GRID grid.33763.32, The School of Life Science, , Tianjin University, ; Tianjin, 300072 People’s Republic of China
                [4 ]ISNI 0000 0000 9792 1228, GRID grid.265021.2, The School of Graduate, , Tianjin Medical University, ; Tianjin, 300072 People’s Republic of China
                [5 ]ISNI 0000 0004 1757 9434, GRID grid.412645.0, Department of Cardiothoracic Surgery, , Tianjin Medical University General Hospital, ; Anshan Road 154, Heping District, Tianjin, 300052 People’s Republic of China
                Author information
                http://orcid.org/0000-0002-9183-6094
                Article
                985
                10.1186/s12935-019-0985-9
                6794789
                31636510
                964131c3-d6cf-4f8c-b9ca-2e238b50c1bb
                © The Author(s) 2019

                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
                : 21 March 2019
                : 30 September 2019
                Categories
                Primary Research
                Custom metadata
                © The Author(s) 2019

                Oncology & Radiotherapy
                esophageal carcinoma,cancer,circrnas,circpvt1,apoptosis,te-10,mir-4663,si-rna
                Oncology & Radiotherapy
                esophageal carcinoma, cancer, circrnas, circpvt1, apoptosis, te-10, mir-4663, si-rna

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