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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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      Is Open Access

      MiR-29a function as tumor suppressor in cervical cancer by targeting SIRT1 and predict patient prognosis

      research-article
      1 , 2 , 3 , 1
      OncoTargets and therapy
      Dove
      miR-29a, cervical cancer, SIRT1, tumor suppressor, EMT

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          Abstract

          Introduction

          Cervical cancer is the second most frequently malignant tumors in females and metastasis is a challenge of the treatment of cervical cancer. MiR-29a is usually low expressed in several tumors and its functions in cervical cancer remain unclear.

          Patients and methods

          The quantitative real-time polymerase chain reaction was employed to assess the expression of miR-29a and the Sirtuin-1 (SIRT1). Cell metastatic ability was assessed using Transwell and Western blot assays. The dual-luciferase reporter assay was performed to verify that miR-29a targeted to the 3’-untranslated region (UTR) of SIRT1 mRNA.

          Results

          MiR-29a was low expressed in cervical cancer and downregulation of miR-29a was associated with poor outcome. MiR-29a regulated the expression of SIRT1 by targeting to its 3’-UTR of mRNA in HeLa cells. SIRT1 was upregulated in cervical cancer tissues and cells in comparison with the non-tumor tissues and normal cells. Upregulation of SIRT1 predicted worse outcome of cervical cancer patients. MiR-29a was participated in the migration, invasion and epithelial–mesenchymal transition (EMT) in cervical cancer through directly targeting to the 3’-UTR of SIRT1 mRNA. SIRT1 reversed partial roles of miR-29a on metastasis in cervical cancer.

          Conclusion

          miR-29a suppressed migration, invasion and EMT by directly targeting to SIRT1 in cervical cancer. The newly identified miR-29a/SIRT1 axis provides novel insight into the pathogenesis of cervical cancer.

          Most cited references32

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          Role of SIRT1 in Modulating Acetylation of the Sarco-Endoplasmic Reticulum Ca 2+ -ATPase in Heart Failure

          SERCA2a, sarco-endoplasmic reticulum Ca 2+ -ATPase, is a critical determinant of cardiac function. Reduced level and activity of SERCA2a are major features of heart failure (HF). Accordingly, intensive efforts have been made to develop efficient modalities for SERCA2a activation. We showed that the activity of SERCA2a is enhanced by post-translational modification (PTM) with small ubiquitin-like modifier 1 (SUMO1). However, the roles of other PTMs on SERCA2a are still unknown. In this study, we aim to assess the role of lysine acetylation on SERCA2a function and determine whether inhibition of lysine acetylation can improve cardiac function in the setting of HF. The acetylation of SERCA2a was significantly increased in failing hearts of humans, mice, and pigs, which is associated with the reduced level of SIRT1, a class III histone deacetylase. Down-regulation of SIRT1 increased the SERCA2a acetylation, which in turn led to SERCA2a dysfunction and cardiac defects at baseline. In contrast, pharmacological activation of SIRT1 reduced the SERCA2a acetylation, which was accompanied by recovery of SERCA2a function and cardiac defects in failing hearts. Lysine 492 (K492) was of critical importance for the regulation of SERCA2a activity via acetylation. Acetylation at K492 significantly reduced the SERCA2a activity, presumably through interfering with the binding of ATP to SERCA2a. In failing hearts, acetylation at K492 appeared to be mediated by p300, a histone acetyltransferase. These results indicate that acetylation/deacetylation at K492, which is regulated by SIRT1 and p300, is critical for the regulation of SERCA2a activity in hearts. Pharmacological activation of SIRT1 can restore SERCA2a activity through deacetylation at K492. These findings might provide a novel strategy for the treatment of HF.
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            Significance of lymph node ratio in defining risk category in node-positive early stage cervical cancer.

            The ratio of positive to negative lymph nodes, or lymph node ratio (LNR), is an important prognostic factor in several solid tumors. The objective of this study was to determine if LNR can be used to define a high-risk category of patients with node-positive early stage cervical cancer.
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              Sirt1 Promotes Osteogenic Differentiation and Increases Alveolar Bone Mass via Bmi1 Activation in Mice

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                Author and article information

                Journal
                Onco Targets Ther
                Onco Targets Ther
                OTT
                ott
                OncoTargets and therapy
                Dove
                1178-6930
                26 August 2019
                2019
                : 12
                : 6917-6925
                Affiliations
                [1 ]Department of Gynaecology, Shengli Oil Centre Hospital , Dongying, People’s Republic of China
                [2 ]Department of Joint Surgery, Shengli Oil Center Hospital , Dongying, People’s Republic of China
                [3 ]Department of Gynecology, Dongying District People’s Hospital , Dongying, People’s Republic of China
                Author notes
                Correspondence: Qiang Li Department of Gynaecology, Shengli Oil Centre Hospital , No. 31 Jinan Road, Dongying District, Dongying District257000, People’s Republic of ChinaTel +86 158 8997 7885Email rllkumf@163.com
                Article
                218043
                10.2147/OTT.S218043
                6717154
                ef6d2d19-79a5-49b8-92c8-b3552ee1b9c0
                © 2019 Nan 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. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 02 June 2019
                : 31 July 2019
                Page count
                Figures: 5, References: 38, Pages: 9
                Categories
                Original Research

                Oncology & Radiotherapy
                mir-29a,cervical cancer,sirt1,tumor suppressor,emt
                Oncology & Radiotherapy
                mir-29a, cervical cancer, sirt1, tumor suppressor, emt

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