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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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      Long noncoding RNA SNHG15 serves as an oncogene and predicts poor prognosis in epithelial ovarian cancer

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          Abstract

          Objective

          This study aims to investigate the functional role of long noncoding RNA SNHG15 in epithelial ovarian cancer (EOC).

          Materials and methods

          The expression of SNHG15 was measured in EOC cells and tissues using qRT-PCR. The correlation of SNHG15 expression and the clinicopathological characters was statistically analyzed. The prognosis of patients with different clinical features in the high/low SNHG15 expression groups were calculated. Moreover, univariate and multivariate Cox regression analyses were performed to identify the risk factors for poor overall survival (OS) and progression-free survival (PFS). The effect of SNHG15 on the migration and invasion was evaluated using Transwell and Matrigel, respectively. The proliferation ability of EOC cells was tested using colony formation and MTT assay. The influence of SNHG15 on the cisplatin resistance was detected by measuring cell inhibition rate and cell viability.

          Results

          SNHG15 was upegulated in EOC cells and tissues. High SNHG15 expression was correlated with EOC progression and predicted poor OS and PFS in different subgroups of EOC patients. Moreover, multivariate Cox regression analysis defined high SNHG15 expression as an independent risk factor for poor OS and PFS. Furthermore, functional assays showed that the overexpression of SNHG15 promoted migration and invasion, while the loss of SNHG15 suppressed migration and invasion. Furthermore, the proliferation of EOC cells was improved after the ectopic expression of SNHG15, which was suppressed with SNHG15 deficiency. In addition, cisplatin-resistant EOC cells were established for detecting the effect of SNHG15 on EOC chemoresistance. The results showed that cisplatin-resistant EOC cells exhibited much higher levels of SNHG15 expression than controls, and SNHG15 contributed to the chemoresistance of EOC cells.

          Conclusion

          This study confirms that SNHG15 contributes to the migration, invasion, proliferation, and chemoresistance of EOC. SNHG15 may serve as a potential therapeutic target and prognostic biomarker of EOC patients.

          Most cited references27

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          The bright side of dark matter: lncRNAs in cancer.

          The traditional view of genome organization has been upended in the last decade with the discovery of vast amounts of non-protein-coding transcription. After initial concerns that this "dark matter" of the genome was transcriptional noise, it is apparent that a subset of these noncoding RNAs are functional. Long noncoding RNA (lncRNA) genes resemble protein-coding genes in several key aspects, and they have myriad molecular functions across many cellular pathways and processes, including oncogenic signaling. The number of lncRNA genes has recently been greatly expanded by our group to triple the number of protein-coding genes; therefore, lncRNAs are likely to play a role in many biological processes. Based on their large number and expression specificity in a variety of cancers, lncRNAs are likely to serve as the basis for many clinical applications in oncology.
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            Minireview: human ovarian cancer: biology, current management, and paths to personalizing therapy.

            More than 90% of ovarian cancers have been thought to arise from epithelial cells that cover the ovarian surface or, more frequently, line subserosal cysts. Recent studies suggest that histologically similar cancers can arise from the fimbriae of Fallopian tubes and from deposits of endometriosis. Different histotypes are observed that resemble epithelial cells from the normal Fallopian tube (serous), endometrium (endometrioid), cervical glands (mucinous), and vaginal rests (clear cell) and that share expression of relevant HOX genes which drive normal gynecological differentiation. Two groups of epithelial ovarian cancers have been distinguished: type I low-grade cancers that present in early stage, grow slowly, and resist conventional chemotherapy but may respond to hormonal manipulation; and type II high-grade cancers that are generally diagnosed in advanced stage and grow aggressively but respond to chemotherapy. Type I cancers have wild-type p53 and BRCA1/2, but have frequent mutations of Ras and Raf as well as expression of IGFR and activation of the phosphatidylinositol-3-kinase (PI3K) pathway. Virtually all type II cancers have mutations of p53, and almost half have mutation or dysfunction of BRCA1/2, but other mutations are rare, and oncogenesis appears to be driven by amplification of several growth-regulatory genes that activate the Ras/MAPK and PI3K pathways. Cytoreductive surgery and combination chemotherapy with platinum compounds and taxanes have improved 5-yr survival, but less than 40% of all stages can be cured. Novel therapies are being developed that target high-grade serous cancer cells with PI3Kness or BRCAness as well as the tumor vasculature. Both in silico and animal models are needed that more closely resemble type I and type II cancers to facilitate the identification of novel targets and to predict response to combinations of new agents.
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              LncRNA MALAT1 promotes proliferation and metastasis in epithelial ovarian cancer via the PI3K-AKT pathway.

              The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that plays a key role in the malignant phenotype of tumors. Although abnormal regulation of lncRNA MALAT1 impacts clinical prognostic and tumor metastasis, its function remains unclear in ovarian cancer.
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                Author and article information

                Journal
                Onco Targets Ther
                Onco Targets Ther
                OncoTargets and Therapy
                OncoTargets and therapy
                Dove Medical Press
                1178-6930
                2019
                19 December 2018
                : 12
                : 101-111
                Affiliations
                [1 ]Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, People’s Republic of China
                [2 ]Department of School Hospital, Changchun University of Chinese Medicine, Changchun 130033, Jilin, People’s Republic of China
                [3 ]Department of Obstetrics and Gynaecology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, People’s Republic of China, junbaoliujilin@ 123456sohu.com
                Author notes
                Correspondence: Junbao Liu, Department of Obstetrics and Gynaecology, China–Japan Union Hospital of Jilin University, No 126, Xiantai Street, Changchun 130033, Jilin, People’s Republic of China, Tel +86 431 8499 4575, Email junbaoliujilin@ 123456sohu.com
                [*]

                These authors contributed equally to this work

                Article
                ott-12-101
                10.2147/OTT.S182657
                6304080
                30588034
                4714fe10-79f5-410d-a967-0fd87c3eed64
                © 2019 Qu et al. 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.

                History
                Categories
                Original Research

                Oncology & Radiotherapy
                noncoding rna,ovarian cancer,proliferation,metastasis,chemoresistance
                Oncology & Radiotherapy
                noncoding rna, ovarian cancer, proliferation, metastasis, chemoresistance

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