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      Reduced microRNA-451 expression in eutopic endometrium contributes to the pathogenesis of endometriosis

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          Abstract

          BACKGROUND

          Endometriosis (EMs) is a chronic and recurrent, but benign, disease in women of reproductive age, and EMs patients have a high risk of developing gynecological tumors and autoimmune disorders. The etiology of EMs is not clear. Certain genetic markers in the eutopic endometrium are key in the pathogenesis of EMs. MicroRNAs (miRNAs) are implicated in several biological processes, such as cell proliferation, differentiation, and apoptosis. MiR-451 is interesting, as it acts as a tumor suppressor and is relevant to the poor prognosis of cancers.

          AIM

          To evaluate the expression levels and role of miR-451 in the eutopic endometrium and predict possible targets of miR-451 and related signaling pathways.

          METHODS

          Quantitative real-time polymerase chain reaction was used to evaluate miR-451 expression in cultured cell lines as well as in pathologic tissues from 40 patients with EMs and 20 donors with no history of the disease (controls). Cell Counting Kit-8 and flow cytometric assays were performed to determine cell proliferation and survival rates after transfection with miR-451 mimics and siRNAs. MiR-451 targets were predicted using miRDB and miRcode target-predicting databases.

          RESULTS

          We observed lower miR-451 levels in eutopic endometrial tissues from patients with EMs than in control tissues, and this difference was not related to the American Society for Reproductive Medicine stage. Ectopic overexpression of miR-451 in eutopic cells induced apoptosis and inhibited cell proliferation. SiRNA-mediated miR-451 knockdown reversed these effects. Using miRDB and miRcode, we identified 12 potential miR-451 target genes. We hypothesize that the expression of YWHAZ, OSR1, TTN, and CDKN2D may be regulated by miR-451 and be involved in disease pathogenesis.

          CONCLUSION

          Reduced miR-451 expression in the eutopic endometrium contributes to the pathogenesis of EMs by promoting cell proliferation and reducing apoptosis. Thus, miR-451 is a novel biomarker for EMs. YWHAZ, OSR1, TTN, and CDKN2D are potential target genes of miR-451 and may have key roles in this disease.

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          Most cited references 27

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          Endometriosis: epidemiology and aetiological factors.

          Estimates of the frequency of endometriosis vary widely. Based on the few reliable data, the prevalence of the condition can reasonably be assumed to be around 10%. Although no consistent information is available on the incidence of the disease, temporal trends suggest an increase among women of reproductive age. This could be explained-at least in part-by changing reproductive habits. Numerous epidemiological studies have indicated that nulliparous women and women reporting short and heavy menstrual cycles are at increased risk of developing endometriosis; data on other risk factors are less consistent. These epidemiological findings strongly support the menstrual reflux hypothesis. Additional evidence in favour of this theory includes the demonstration of viable endometrial cells in the menstrual effluent and peritoneal fluid, experimental implantation and growth of endometrium within the peritoneal cavity, observation of some degree of retrograde menstruation in most women undergoing laparoscopy during menses, and an association between obstructed menstrual outflow and endometriosis.
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            Metastatic or Embolic Endometriosis, due to the Menstrual Dissemination of Endometrial Tissue into the Venous Circulation.

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              High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis.

              Women with endometriosis may also have associated disorders related to autoimmune dysregulation or pain. This study examined whether the prevalence of autoimmune, chronic pain and fatigue and atopic disorders is higher in women with endometriosis than in the general female population. A cross-sectional survey was conducted in 1998 by the Endometriosis Association of 3680 USA members with surgically diagnosed endometriosis. Almost all responders had pain (99%), and many reported infertility (41%). Compared with published rates in the general USA female population, women with endometriosis had higher rates of hypothyroidism (9.6 versus 1.5%, P < 0.0001), fibromyalgia (5.9 versus 3.4%, P < 0.0001), chronic fatigue syndrome (4.6 versus 0.03%, P < 0.0001), rheumatoid arthritis (1.8 versus 1.2%, P = 0.001), systemic lupus erythematosus (0.8 versus 0.04%, P < 0.0001), Sjögren's syndrome (0.6 versus 0.03%, P < 0.0001) and multiple sclerosis (0.5 versus 0.07%, P < 0.0001), but not hyperthyroidism or diabetes. Allergies and asthma were more common among women with endometriosis alone (61%, P < 0.001 and 12%, P < 0.001 respectively) and highest in those with fibromyalgia or chronic fatigue syndrome (88%, P < 0.001 and 25%, P < 0.001 respectively) than in the USA female population (18%, P < 0.001 and 5%, P < 0.001 respectively). Hypothyroidism, fibromyalgia, chronic fatigue syndrome, autoimmune diseases, allergies and asthma are all significantly more common in women with endometriosis than in women in the general USA population.
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                Author and article information

                Contributors
                Journal
                World J Clin Cases
                WJCC
                World Journal of Clinical Cases
                Baishideng Publishing Group Inc
                2307-8960
                26 August 2019
                26 August 2019
                : 7
                : 16
                : 2155-2164
                Affiliations
                Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110042, Liaoning Province, China
                Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110042, Liaoning Province, China
                Department of Surgical Oncology and General Surgery, First Affiliated Hospital of China Medical University, Shenyang 110042, Liaoning Province, China
                Department of Surgical Oncology and General Surgery, First Affiliated Hospital of China Medical University, Shenyang 110042, Liaoning Province, China
                Department of Gynecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China. wangdb_cmu@ 123456126.com
                Author notes

                Author contributions: Gao S performed the majority of the experiments and analyzed the data; Liu S and Deng P performed the molecular investigations; Wang DB conceived and designed the experiments; Gao S and Gao ZM wrote the manuscript.

                Corresponding author: Dan-Bo Wang, MD, Professor, Department of Gynecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, No. 44, Xiaoheyan Road, Dadong District, Shenyang 110042, Liaoning Province, China. wangdb_cmu@ 123456126.com

                Telephone: +86-13840265165

                Article
                jWJCC.v7.i16.pg2155
                10.12998/wjcc.v7.i16.2155
                6718782
                ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                Categories
                Basic Study

                apoptosis, pathogenesis, proliferation, endometriosis, mir-451

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