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      Hsa_circ_0086414 Might Be a Diagnostic Biomarker of Oral Squamous Cell Carcinoma

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          Abstract

          Background

          Circular RNAs (circRNAs), a newly-discovered class of non-coding RNAs, have a significant role in the progression of cancers, but the effect of hsa_circ_0086414 in human oral squamous cell carcinoma (OSCC) is still unclear.

          Material/Methods

          The circRNAs expression profile in OSCC tissue samples was assessed by high-throughput sequencing. The hsa_circ_0086414 expression level in 55 paired OSCC tissue samples and 2 kinds of OSCC cells was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, the correlation between the hsa_circ_0086414 expression and clinicopathological characteristics of individuals with OSCC was studied. We used receiver operating characteristic (ROC) curves to observe the hsa_circ_0086414 value of diagnosis in OSCC. The network of hsa_circ_0086414-miRNAs-mRNAs was constructed. Gene Ontology (GO), Disease Oncology (DO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out based on sequencing data and bioinformatics predictions.

          Results

          Hsa_circ_0086414 expression in OSCC tissue samples and OSCC cells was first discovered to be significantly downregulated compared with the adjacent healthy tissues (AHTs) and normal (HaCaT) cells, respectively. Moreover, its expression level was significantly correlated with stage in TNM, size of tumor, and lymph node metastasis. The area below the ROC curve was 0.749. Hsa_circ_0086414-miRNAs-mRNAs network analysis and GO, DO, and KEGG analyses all demonstrated that hsa_circ_0086414 is correlated with cancer progression to a certain extent.

          Conclusions

          We discovered that hsa_circ_0086414 might be an essential diagnostic biomarker in OSCC. Furthermore, hsa_circ_0086414 could be a target for OSCC therapy.

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          Most cited references33

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          Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in oral cancer.

          In the last few years, microRNAs (miRNA) have started a revolution in molecular biology and emerged as key players in the carcinogenesis. They have been identified in various tumor types, showing that different sets of miRNAs are usually deregulated in different cancers. To identify the miRNA signature that was specific for oral squamous cell carcinoma (OSCC), we first examined expression profiles of 148 miRNAs in a panel of 18 OSCC cell lines and the immortalized oral keratinocyte line RT7 as a control. Compared with RT7, the expression of 54 miRNAs (36.5%) was frequently down-regulated in OSCC lines ( or=66.7% of 18 lines). Among these 54 miRNAs, we further analyzed four of these miRNAs (i.e., miR-34b, miR-137, miR-193a, and miR-203), located around CpG islands, to identify tumor-suppressive miRNAs silenced through aberrant DNA methylation. The expression of those four genes was restored by treatment with 5-aza-2'-deoxycytidine in OSCC cells lacking their expression. In addition, expression levels of the four miRNAs were inversely correlated with their DNA methylation status in the OSCC lines. In primary tumors of OSCC with paired normal oral mucosa, down-regulation of miRNA expression through tumor-specific hypermethylation was more frequently observed for miR-137 and miR-193a than for miR-34b and miR-203. Moreover, the ectopic transfection of miR-137 or miR-193a into OSCC lines lacking their expressions significantly reduced cell growth, with down-regulation of the translation of cyclin-dependent kinase 6 or E2F transcription factor 6, respectively. Taken together, our results clearly show that miR-137 and miR-193a are tumor suppressor miRNAs epigenetically silenced during oral carcinogenesis.
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            Isolation and characterization of Sendai virus DI-RNAs.

            When passaged at high multiplicity, four strains of Sendai virus all showed evidence that they contained defective interfering (DI) particles. RNA isolated from nucleocapsids of cells infected with the high multiplicity passage stocks was found to consist of only minor amounts of nondefective genome length RNA and major amounts of smaller RNAs, the DI-RNAs. These DI-RNAs were found to have unusual and variable sedimentation properties in sucrose gradients, but were found to represent unique segments of the viral genome by length measurements in the electron microscope and by hybridization. A striking feature of the DI-RNAs is their ability to form circular structures, indicating that the ends of the DI-RNA are complementary. The implications of this finding in terms of the mechanism of genome replication is discussed.
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              CircDOCK1 suppresses cell apoptosis via inhibition of miR-196a-5p by targeting BIRC3 in OSCC

              Oral squamous cell carcinoma (OSCC) is the most frequent oral cancer in the world, accounting for more than 90% of all oral cancer diagnosis. Circular RNAs (circRNAs) are large types of non-coding RNAs, demonstrating a great capacity of regulating the expression of genes. However, most of the functions of circRNAs are still unknown. Recent research revealed that circRNAs could serve as a miRNA-sponge, consequently regulating the expression of target genes indirectly, including oncogenes. In this study, we built an apoptotic model with TNF-α, and then we confirmed a circRNA associated with the apoptosis of OSCC cells, circDOCK1 by comparing the expression profile of circRNAs in an apoptotic model with that in untreated OSCC cells. We ascertained the presence of circDOCK1 with qRT-PCR and circRNA sequencing. The knockdown of the expression of circDOCK1 led to the increase of apoptosis. Utilizing multiple bioinformatics methods, we predicted the interactions among circRNAs, miRNAs and genes, and built the circDOCK1/miR-196a-5p/BIRC3 axis. Both the silencing of circDOCK1 with small interfering RNA and the upregulation of the expression of miR-196a-5p with mimics led OSCC cells to increase apoptosis and decrease BIRC3 formation. We further confirmed this outcome by comparing the expression of circDOCK1, miR-196a-5p and BIRC3 in oral squamous carcinoma tissue with those in para-carcinoma tissue, and examining the expression profile of circRNAs in oral squamous carcinoma tissue and para-carcinoma tissue with microarray. Our results demonstrated that circDOCK1 regulated BIRC3 expression by functioning as a competing endogenous RNA (ceRNA) and participated in the process of OSCC apoptosis. Thus, we propose that circDOCK1 could represent a novel potential biomarker and therapeutic target of OSCC.
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                Author and article information

                Journal
                Med Sci Monit
                Med. Sci. Monit
                Medical Science Monitor
                Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
                International Scientific Literature, Inc.
                1234-1010
                1643-3750
                2020
                14 January 2020
                : 26
                : e919383-1-e919383-13
                Affiliations
                VIP Department, School of Stomatology, China Medical University, Shenyang, Liaoning, P.R. China
                Author notes
                Corresponding Author: Zhong-Ti Zhang, e-mail: zhangzhongti@ 123456163.com
                [A]

                Study Design

                [B]

                Data Collection

                [C]

                Statistical Analysis

                [D]

                Data Interpretation

                [E]

                Manuscript Preparation

                [F]

                Literature Search

                [G]

                Funds Collection

                Article
                919383
                10.12659/MSM.919383
                6978993
                31933490
                8c3b6211-6607-47be-a358-6cdd40bcbdd6
                © Med Sci Monit, 2020

                This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International ( CC BY-NC-ND 4.0)

                History
                : 13 August 2019
                : 27 October 2019
                Categories
                Clinical Research

                biological markers,diagnosis,mouth neoplasms
                biological markers, diagnosis, mouth neoplasms

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