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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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      Matrix metalloproteinase-7 may serve as a novel biomarker for cervical cancer

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          Abstract

          Background

          The biological and clinical significance of matrix metalloproteinase-7 (MMP-7) in cervical cancer remains unknown. Here, we investigated the function of MMP-7 in cervical cancer cells and evaluated its clinical significance in both tissues and serum from cervical cancer patients.

          Methods

          First, we analyzed the expression of MMP-7 in cervical cancer using Oncomine microarray data and examined its expression in cervical tissues by quantitative real-time polymerase chain reaction and Western blotting. Second, we utilized gene silencing to explore the role of MMP-7 in cells. Finally, we examined the MMP-7 levels in patients with cervical cancer and normal serum by enzyme-linked immunosorbent assay. Moreover, we further investigated the relationship between MMP-7 expression and pathological features.

          Results

          The mRNA and protein MMP-7 levels were higher in cervical cancer tissues than in healthy controls. Silencing of MMP-7 significantly decreased cervical cancer cell proliferation, migration, and invasion. The serum MMP-7 levels were significantly higher in cervical cancer patients than in healthy subjects ( P<0.01). Further, higher MMP-7 expression was associated with increased lymph metastasis ( P=0.021), pathological grade ( P=0.039, P=0.047), and clinical stage ( P=0.049, P=0.046).

          Conclusion

          MMP-7 appears to act as an oncogene in cervical cancer cells and is involved in cell proliferation, migration, and invasion. MMP-7 expression was significantly higher in the tissue and serum of cervical cancer patients compared to healthy individuals and was correlated with increased pathalogical grade, clinical stage, and lymph metastasis. Therefore, our data provide novel evidence that MMP-7 may be a clinically relevant biomarker for cervical cancer.

          Most cited references37

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          Cancer epigenetics: linking basic biology to clinical medicine.

          Cancer evolution at all stages is driven by both epigenetic abnormalities as well as genetic alterations. Dysregulation of epigenetic control events may lead to abnormal patterns of DNA methylation and chromatin configurations, both of which are critical contributors to the pathogenesis of cancer. These epigenetic abnormalities are set and maintained by multiple protein complexes and the interplay between their individual components including DNA methylation machinery, histone modifiers, particularly, polycomb (PcG) proteins, and chromatin remodeling proteins. Recent advances in genome-wide technology have revealed that the involvement of these dysregulated epigenetic components appears to be extensive. Moreover, there is a growing connection between epigenetic abnormalities in cancer and concepts concerning stem-like cell subpopulations as a driving force for cancer. Emerging data suggest that aspects of the epigenetic landscape inherent to normal embryonic and adult stem/progenitor cells may help foster, under the stress of chronic inflammation or accumulating reactive oxygen species, evolution of malignant subpopulations. Finally, understanding molecular mechanisms involved in initiation and maintenance of epigenetic abnormalities in all types of cancer has great potential for translational purposes. This is already evident for epigenetic biomarker development, and for pharmacological targeting aimed at reversing cancer-specific epigenetic alterations.
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            Matrix metalloproteinases in kidney homeostasis and diseases.

            Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that have been increasingly linked to both normal physiology and abnormal pathology in the kidney. Collectively able to degrade all components of the extracellular matrix, MMPs were originally thought to antagonize the development of fibrotic diseases solely through digestion of excessive matrix. However, increasing evidence has shown that MMPs play a wide variety of roles in regulating inflammation, epithelial-mesenchymal transition, cell proliferation, angiogenesis, and apoptosis. We now have robust evidence for MMP dysregulation in a multitude of renal diseases including acute kidney injury, diabetic nephropathy, glomerulonephritis, inherited kidney disease, and chronic allograft nephropathy. The goal of this review is to summarize current findings regarding the role of MMPs in kidney diseases as well as the mechanisms of action of this family of proteases.
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              Matrilysin (matrix metalloproteinase-7) mediates E-cadherin ectodomain shedding in injured lung epithelium.

              Matrilysin (matrix metalloproteinase-7) is highly expressed in lungs of patients with pulmonary fibrosis and other conditions associated with airway and alveolar injury. Although matrilysin is required for closure of epithelial wounds ex vivo, the mechanism of its action in repair is unknown. We demonstrate that matrilysin mediates shedding of E-cadherin ectodomain from injured lung epithelium both in vitro and in vivo. In alveolar-like epithelial cells, transfection of activated matrilysin resulted in shedding of E-cadherin and accelerated cell migration. In vivo, matrilysin co-localized with E-cadherin at the basolateral surfaces of migrating tracheal epithelium, and the reorganization of cell-cell junctions seen in wild-type injured tissue was absent in matrilysin-null samples. E-cadherin ectodomain was shed into the bronchoalveolar lavage fluid of bleomycin-injured wild-type mice, but was not shed in matrilysin-null mice. These findings identify E-cadherin as a novel substrate for matrilysin and indicate that shedding of E-cadherin ectodomain is required for epithelial repair.
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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
                2018
                20 July 2018
                : 11
                : 4207-4220
                Affiliations
                Department of Obstetrics and Gynaecology, Ningbo First Hospital, Ningbo, Zhejiang, People’s Republic of China, cuilining@ 123456hotmail.com
                Author notes
                Correspondence: Lining Cui, Department of Obstetrics and, Gynaecology, Ningbo First Hospital, 9 Liuting Street, Ningbo, Zhejiang, 315000, People’s Republic of China, Email cuilining@ 123456hotmail.com
                [*]

                These authors contributed equally to this work

                Article
                ott-11-4207
                10.2147/OTT.S160998
                6055895
                cf888a19-6736-4e2a-8dea-d4dfae4e7399
                © 2018 Zhu 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
                cervical cancer,matrix metalloproteinase-7,biomarker,migration,invasion
                Oncology & Radiotherapy
                cervical cancer, matrix metalloproteinase-7, biomarker, migration, invasion

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