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      Circular RNA circ_HIPK3 is down-regulated and suppresses cell proliferation, migration and invasion in osteosarcoma

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          Abstract

          Circular RNA (circRNA) is associated with human cancers, however, few studies have reported its value in the diagnosis and prognosis prediction of osteosarcoma (OS). In this study, we investigated the expression level of eight selected cancer-related circRNAs including circ-Cdr1as, circ_HIPK3 and circ-ITCH in OS cell lines, tissues and plasmas by quantitative real-time polymerase chain reaction (qRT-PCR) and found that only circ_HIPK3 could stably down-regulate in the OS cell lines, tissues and plasmas than the corresponding controlled. One-way analysis of variance was further conducted to analyze the relationship between circ_HIPK3 expression level and clinic pathological factors of OS patients. Receiver operating characteristic (ROC) curve was built to evaluate the diagnostic values of circ_HIPK3. Circ_HIPK3 expression was significantly correlated with Enneking stage (P=0.042) and lung metastasis (P=0.036). The area under the ROC curve was 0.783 and the sensitivity and specificity were 0.56 and 0.84, respectively. Kaplan-Maier analysis also showed that lower expression of circ_HIPK3 correlated with shorter overall survival time and poor prognosis of OS patients. Besides, function analysis demonstrated that circHIPK3 overexpression significantly suppressed OS cell proliferation, migration and invasion in vitro. Overall, our data suggest that circ_HIPK3 may become a novel potential biomarker for diagnosis and treatment target of OS.

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          The circular RNA Cdr1as, via miR-7 and its targets, regulates insulin transcription and secretion in islet cells

          Among the identified thousands of circular RNAs (circRNA) in humans and animals, Cdr1as (also known as CiRS-7) was recently demonstrated to act as a powerful miR-7 sponge/inhibitor in developing midbrain of zebrafish, suggesting a novel mechanism for regulating microRNA functions. MiR-7 is abundantly expressed in islet cells, but overexpressing miR-7 in transgenic mouse β cells causes diabetes. Therefore, we infer that Cdr1as expression may inhibit miR-7 function in islet cells, which in turn improves insulin secretion. Here, we show the first characterization of Cdr1as expression in islet cells, which was upregulated by long-term forskolin and PMA stimulation, but not high glucose, indicating the involvement of cAMP and PKC pathways. Remarkably, both insulin content and secretion were significantly increased by overexpression of Cdr1as in islet cells. We further identified a new target Myrip in the Cdr1as/miR-7 pathway that regulates insulin granule secretion, and also another target Pax6 that enhances insulin transcription. Taken together, our findings revealed the effects of the strongly interacting pair of Cdr1as/miR-7 on insulin secretion, which may become a new target for improving β cell function in diabetes.
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            Circular Noncoding RNA HIPK3 Mediates Retinal Vascular Dysfunction in Diabetes Mellitus.

            The vascular complications of diabetes mellitus are the major causes of morbidity and mortality among people with diabetes. Circular RNAs are a class of endogenous noncoding RNAs that regulate gene expression in eukaryotes. In this study, we investigated the role of circular RNA in retinal vascular dysfunction induced by diabetes mellitus.
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              Emerging roles of circRNA_001569 targeting miR-145 in the proliferation and invasion of colorectal cancer

              Circular RNAs (circRNAs), a large class of RNAs, have recently shown huge capabilities as gene regulators in mammals. Some of them bind with microRNAs (miRNAs) and act as natural miRNA sponges to inhibit related miRNAs’ activities. Here we showed that hsa_circ_001569 acted as a positive regulator in cell proliferation and invasion of colorectal cancer (CRC). Moreover, hsa_circ_001569 was identified as a sponge of miR-145 and up-regulated miR-145 functional targets E2F5, BAG4 and FMNL2. In CRC tissues, circ_001569 negatively correlated with miR-145, and miR-145 correlated negatively with E2F5, BAG4 and FMNL2 expressions. Our study reveals a novel regulatory mechanism of circ_001569 in cell proliferation and invasion in CRC, provides a comprehensive landscape of circ_001569 that will facilitate further biomarker discoveries in the progression of CRC.
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                Author and article information

                Journal
                J Cancer
                J Cancer
                jca
                Journal of Cancer
                Ivyspring International Publisher (Sydney )
                1837-9664
                2018
                26 April 2018
                : 9
                : 10
                : 1856-1862
                Affiliations
                [1 ]Department of Orthopaedic Surgery, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, PR China
                [2 ]Institute of Bone Tumor Affiliated to Tongji University School of Medicine, Shanghai 200072, PR China
                Author notes
                ✉ Corresponding author: Zhang Chun-Lin, MD, Department of Orthopaedic Surgery, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, 301, Yan-chang Middle Road, Shanghai 200072, China. E-mail: shzhangchunlin123@ 123456163.com . Fax: +86 13761904091 and Zhu Kun-Peng, MD, Department of Orthopaedic Surgery, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, 301, Yan-chang Middle Road, Shanghai 200072, China. E-mail: zhukunpeng@ 123456tongji.edu.cn . Fax: +86 15216636683.

                *These authors contributed equally to this study and share first authorship. They are all considered Co-first authors.

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                jcav09p1856
                10.7150/jca.24619
                5968774
                c36d9f75-db87-43a6-949d-8cd51bc0170f
                © Ivyspring International Publisher

                This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 28 December 2017
                : 14 February 2018
                Categories
                Research Paper

                Oncology & Radiotherapy
                circrna,circ_hipk3,osteosarcoma,biomarker,progression
                Oncology & Radiotherapy
                circrna, circ_hipk3, osteosarcoma, biomarker, progression

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