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      LncRNA AWPPH promotes the proliferation, migration and invasion of ovarian carcinoma cells via activation of the Wnt/β-catenin signaling pathway

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          Abstract

          The oncogenic role of the long noncoding RNA associated with poor prognosis of hepatocellular carcinoma (lncRNA AWPPH) was reported in various types of malignancies; however, its involvement in ovarian carcinoma (OC) remains unknown. Thus, the present study investigated the role of AWPPH in OC. The expression of AWPPH in tissues and serum acquired from patients with OC, and healthy controls, was determined via reverse transcription-quantitative polymerase chain reaction. The diagnostic value of serum AWPPH expression was evaluated by receiver operating characteristic curve analysis. Additionally, survival curve analysis was performed to determine the prognostic value of AWPPH for OC. An AWPPH overexpression vector was transfected into OC cell lines. Cell proliferation, migration and invasion were analyzed via Cell Counting Kit-8, Transwell migration and invasion assays, respectively. The expression of β-catenin was investigated via western blotting. It was revealed that the expression levels of AWPPH were significantly upregulated in OC tissues and serum compared with healthy controls. The serum levels of AWPPH were able to effectively diagnose and predict the prognosis of patients with OC. AWPPH overexpression promoted the proliferation, migration and invasion of OC cells, and upregulated β-catenin expression. Treatment with a Wnt agonist markedly altered AWPPH expression; however, inhibition of Wnt suppressed the effects of AWPPH overexpression on proliferation, migration and invasion of OC cells. Therefore, it was revealed that AWPPH may promote OC via activation of the Wnt/β-catenin signaling pathway.

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          Most cited references13

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          Ovarian cancer

          Epithelial ovarian cancer is the commonest cause of gynaecological cancer-associated death. The disease typically presents in postmenopausal women, with a few months of abdominal pain and distension. Most women have advanced disease (International Federation of Gynecology and Obstetrics [FIGO] stage III), for which the standard of care remains surgery and platinum-based cytotoxic chemotherapy. Although this treatment can be curative for most patients with early stage disease, most women with advanced disease will develop many episodes of recurrent disease with progressively shorter disease-free intervals. These episodes culminate in chemoresistance and ultimately bowel obstruction, the most frequent cause of death. For women whose disease continues to respond to platinum-based drugs, the disease can often be controlled for 5 years or more. Targeted treatments such as antiangiogenic drugs or poly (ADP-ribose) polymerase inhibitors offer potential for improved survival. The efficacy of screening, designed to detect the disease at an earlier and curable stage remains unproven, with key results expected in 2015. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            Wnt/beta-catenin signaling in cancer stemness and malignant behavior.

            Stem cells are defined by their intrinsic capacity to self-renew and differentiate. Cancer stem cells retain both these features but have lost homeostatic mechanisms which maintain normal cell numbers. The canonical Wnt/beta-catenin signaling pathway plays a central role in modulating the delicate balance between stemness and differentiation in several adult stem cell niches such as the hair follicles in the skin, the mammary gland, and the intestinal crypt. Accordingly, constitutive Wnt signaling activation, resulting from mutations in genes encoding its downstream components, underlies tumorigenesis in these tissues. In the majority of sporadic colorectal cancer cases, the rate-limiting event is either loss of APC function or oncogenic beta-catenin mutations. However, although the presence of these initiating mutations would predict nuclear beta-catenin accumulation throughout the tumor mass, heterogeneous intracellular distributions of this key Wnt signaling molecule are observed within primary tumors and their metastases. In particular, tumor cells located at the invasive front and those migrating into the adjacent stromal tissues show nuclear beta-catenin staining. Hence, different levels of Wnt signaling activity reflect tumor heterogeneity and are likely to account for distinct cellular activities such as proliferation and epithelial-mesenchymal transitions, which prompt tumor growth and malignant behavior, respectively. Several intrinsic (cell-autonomous and/or autocrine) and extrinsic (paracrine, derived from the tumor microenvironment) factors may explain this heterogeneity of Wnt/beta-catenin signaling activity within the tumor mass.
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              Long noncoding RNAs (lncRNAs) and the molecular hallmarks of aging

              During aging, progressive deleterious changes increase the risk of disease and death. Prominent molecular hallmarks of aging are genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, cellular senescence, stem cell exhaustion, and altered intercellular communication. Long noncoding RNAs (lncRNAs) play important roles in a wide range of biological processes, including age-related diseases like cancer, cardiovascular pathologies, and neurodegenerative disorders. Evidence is emerging that lncRNAs influence the molecular processes that underlie age-associated phenotypes. Here, we review our current understanding of lncRNAs that control the development of aging traits.
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                Author and article information

                Journal
                Mol Med Rep
                Mol Med Rep
                Molecular Medicine Reports
                D.A. Spandidos
                1791-2997
                1791-3004
                May 2019
                14 March 2019
                14 March 2019
                : 19
                : 5
                : 3615-3621
                Affiliations
                [1 ]Department of Obstetrics and Gynecology, Yantai Hospital of Traditional Chinese Medicine, Yantai, Shandong 264000, P.R. China
                [2 ]Department of Gynecology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China
                [3 ]Department of Gynecology, Yantai Yeda Hospital, Yantai, Shandong 264000, P.R. China
                Author notes
                Correspondence to: Dr Shaohua Dong, Department of Gynecology, Yantai Yeda Hospital, 11 Taishan Road, Yantai, Shandong 264000, P.R. China, E-mail: skrgnx9@ 123456163.com
                [*]

                Contributed equally

                Article
                mmr-19-05-3615
                10.3892/mmr.2019.10029
                6470830
                30896797
                5e3b5efe-b8dd-4541-a31f-05d532ea8ae9
                Copyright: © Yu et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 20 May 2018
                : 08 February 2019
                Categories
                Articles

                ovarian carcinoma,long noncoding rna,awpph,wnt/β-catenin signaling pathway,proliferation,migration,invasion

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