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      Up-regulated lncRNA XIST contributes to progression of cervical cancer via regulating miR-140-5p and ORC1

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          Abstract

          Background

          The study purpose was to make investigation into the influence of XIST on cervical cancer progression and what’s more its potential mechanism.

          Methods

          The cervical cancer data sets (lncRNA, miRNA, and mRNA) obtained from TCGA were analyzed with the “mixOmics” R package. Then, the expression of XIST, miR-140-5p, and ORC1 were detected using qRT-PCR and western blot in both tissues and cervical cancer cell lines (Hela and C33A) to verify the bioinformatics analyses results. CCK-8 assay, 5-ethynyl-2′-deoxyuridine (EdU) assays, cell cycle assay and cell apoptosis assay were practiced. Besides, immunohistochemistry staining was operated for the detection of the Ki-67, E-cadherin and vimentin expression in cervical cancer tissues and the apoptosis-related proteins expression (c-caspase3, Bcl-2, total PARP and cleaved PARP) was verified through western blot. And in vivo experiments were implemented.

          Results

          MiR-140-5p was down-regulated but XIST and ORC1 were up-regulated in cervical cancer tissues and cell lines. Knocking down of the XIST or ORC1 memorably suppressed cell proliferation, blocked cell cycle, decreased the expression of Bcl-2 while increased the apoptosis rate and the expression of c-caspase3 and cleaved PARP in HeLa and C33A cells. Besides, the results of immunohistochemistry staining showed knocking down the expression of XIST improved the expression levels of E-cadherin and decreased Ki-67 and vimentin expression. And overexpression of miR-140-5p also could inhibit the progression and reverse the influence of XIST and ORC1 in HeLa and C33A cells.

          Conclusion

          Our study indicated the effects of XIST/miR-140-5p/ ORC1 axis on the progression of cervical cancer which will shed new light on epigenetic diagnostics and therapeutics in cervical cancer.

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          Most cited references30

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          mixOmics: An R package for ‘omics feature selection and multiple data integration

          The advent of high throughput technologies has led to a wealth of publicly available ‘omics data coming from different sources, such as transcriptomics, proteomics, metabolomics. Combining such large-scale biological data sets can lead to the discovery of important biological insights, provided that relevant information can be extracted in a holistic manner. Current statistical approaches have been focusing on identifying small subsets of molecules (a ‘molecular signature’) to explain or predict biological conditions, but mainly for a single type of ‘omics. In addition, commonly used methods are univariate and consider each biological feature independently. We introduce mixOmics, an R package dedicated to the multivariate analysis of biological data sets with a specific focus on data exploration, dimension reduction and visualisation. By adopting a systems biology approach, the toolkit provides a wide range of methods that statistically integrate several data sets at once to probe relationships between heterogeneous ‘omics data sets. Our recent methods extend Projection to Latent Structure (PLS) models for discriminant analysis, for data integration across multiple ‘omics data or across independent studies, and for the identification of molecular signatures. We illustrate our latest mixOmics integrative frameworks for the multivariate analyses of ‘omics data available from the package.
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            Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate gastric cancer progression

            Background Long noncoding RNAs (lncRNAs) have recently emerged as important regulators in governing fundamental biological processes, and many of which are likely to have functional roles in tumorigenesis. Maternally expressed gene 3 (MEG3) gene encodes a lncRNA whose expression is lost in an expanding list of primary human tumors and tumor cell lines, however its biological role and regulatory mechanism in gastric cancer (GC) development and progression are poorly defined. Methods Quantitative RT-PCR analysis was used to determine whether aberrant MEG3 expression was associated with GC patients pTNM stage and pM state. Furthermore, the effect of ectopic expression of MEG3 on cell proliferation, migration, invasion and cell apoptosis was assessed by using CCK-8, wound healing, transwell invasion assays and flow cytometric analysis, respectively, in GC cell lines HGC-27 and MGC-803. Moreover, the competing endogenous RNA (ceRNA) activity of MEG3 on miR-181a was investigated via luciferase reporter assay and immunoblot analysis. Results MEG3 is decreased in GC patients and cell lines, and its expression was associated with metastatic GC. Furthermore, ectopic expression of MEG3 in HGC-27 and MGC-803 cells inhibited cell proliferation, migration, invasion, and promoted cell apoptosis, which might be due to MEG3 sequestering oncogenic miR-181 s in GC cells. Furthermore, MEG3 could up-regulated Bcl-2 via its competing endogenous RNA (ceRNA) activity on miR-181a. Conclusions These findings suggest that lncRNA MEG3, a ceRNA of miR-181 s, could regulate gastric carcinogenesis and may serve as a potential target for antineoplastic therapies.
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              Cervical Cancer Prevalence, Incidence and Mortality in Low and Middle Income Countries: A Systematic Review

              Introduction: Cervical cancer rates vary across the world, being highest in Eastern Africa (including Zimbabwe) and lowest in Western Asia. It is the second most common type of cancer in women in the South East Asia region and a major cause of cancer deaths among women of low and middle income countries (LMICs) like Nepal. This review is an attempt to make a comprehensive report of prevalence, incidence and mortality of cervical cancer in LMICs. Methods: The review was conducted applying a computerized search with the Medical Subject Heading (MeSH) major topics “Cervical Cancer”, “Cervical neoplasm” “Epidemiology”, (“prevalence” OR “incidence” OR “mortality”) and “HPV” OR “Human papillomavirus” as MeSH subheading. The search limits were: language (“English”), LMICs, dates (articles published from “1st January 2000 to 31st December 2015”), and species (“Humans”). The search was supplemented by cross-referencing. Publications that met the inclusion criteria were included in the synthesis. Results: Among the 20 studies reviewed; seven were from Africa, seven from Asia, three from South America, and one each from North America, Europe and Oceania. The review found the highest reported age standardized incidence rate as 17.9/100,000/year in Zimbabwe in 2000 and the lowest as 0.11/100,000/year in China in 2006. One study of Nigeria revealed a cervical cancer prevalence of 5.0 per 1,000 in 2012 in the 25-64 year age group. Further, the highest reported age standardized mortality rate was 16/100,000/year in India in 2015 and the lowest 1.8/100,000/year in Colombia in 2013. In addition, coitarche, tobacco smoking, number of sexual partners and family history of cervical cancer were reported as significant risk factors. Conclusion: The study provides a review of reported prevalence, incidence and mortality of cervical cancer in LMICs from 1st January 2000 to 31st December 2015. The scarcity of information reveals a substantial need for further studies on cervical cancer prevalence, incidence and mortality with associated risk factors in LMICs.
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                Author and article information

                Contributors
                chenzilin2009@126.com
                dongcy88@126.com
                yhpifu@163.com
                wenlinlin6688@126.com
                wjylm707@126.com
                shuwang388@163.com
                wuqianyu11@163.com
                chjwang82@163.com
                xiaoyingwu69@163.com
                zyzycpu@126.com
                86-057685120120 , wangshuchun2009@126.com
                Journal
                Cancer Cell Int
                Cancer Cell Int
                Cancer Cell International
                BioMed Central (London )
                1475-2867
                28 February 2019
                28 February 2019
                2019
                : 19
                : 45
                Affiliations
                [1 ]ISNI 0000 0001 0348 3990, GRID grid.268099.c, Department of Obstetrics and Gynecology, Taizhou Hospital of Zhejiang Province, , Wenzhou Medical University, ; No. 150 Ximen Street, Linhai, 317000 Zhejiang China
                [2 ]Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Hangzhou, 310000 Zhejiang China
                [3 ]State Key Laboratory of Experimental Hematology, Institute of Hematology & Hospital of Blood Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020 China
                Author information
                http://orcid.org/0000-0001-7356-8439
                Article
                744
                10.1186/s12935-019-0744-y
                6394057
                30858762
                bb0ec051-af46-4075-8ac2-795942ca7881
                © 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
                : 14 November 2018
                : 31 January 2019
                Categories
                Primary Research
                Custom metadata
                © The Author(s) 2019

                Oncology & Radiotherapy
                xist,mir-140-5p,orc1,cervical cancer cells
                Oncology & Radiotherapy
                xist, mir-140-5p, orc1, cervical cancer cells

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