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      miR-101 sensitizes human nasopharyngeal carcinoma cells to radiation by targeting stathmin 1

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          Abstract

          Radioresistance remains a major problem in the treatment of patients suffering from nasopharyngeal carcinoma (NPC). A better understanding of the mechanisms involved in the induction of radioresistance may provide strategies to improve NPC patients’ response to therapy. The present study aimed to investigate the effect of microRNA (miR)-101 on the radioresistance of NPC cells. Analysis of miR-101 expression levels indicated that miR-101 was downregulated in NPC cell lines. Furthermore, ectopic expression of miR-101 suppressed cell proliferation and enhanced radiosensitivity of NPC cells. Stathmin 1 (STMN1) was additionally verified as a direct functional target of miR-101, which was found to be involved in cell viability, radioresistance and radiation-induced autophagy of NPC cells. In conclusions, the results of the present study suggested that the identified miR-101/STMN1 pathway contributed to the elucidation of the mechanisms of radioresistance in human NPC and that it may represent a potential therapeutic target.

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          Most cited references22

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          gammaH2AX: a sensitive molecular marker of DNA damage and repair.

          Phosphorylation of the Ser-139 residue of the histone variant H2AX, forming gammaH2AX, is an early cellular response to the induction of DNA double-strand breaks. Detection of this phosphorylation event has emerged as a highly specific and sensitive molecular marker for monitoring DNA damage initiation and resolution. Further, analysis of gammaH2AX foci has numerous other applications including, but not limited to, cancer and aging research. Quantitation of gammaH2AX foci has also been applied as a useful tool for the evaluation of the efficacy of various developmental drugs, particularly, radiation modifying compounds. This review focuses on the current status of gammaH2AX as a marker of DNA damage and repair in the context of ionizing radiation. Although the emphasis is on gamma-radiation-induced gammaH2AX foci, the effects of other genotoxic insults including exposure to ultraviolet rays, oxidative stress and chemical agents are also discussed.
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            How does intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients?

            To compare the results of intensity-modulated radiotherapy (IMRT) with those of two-dimensional conventional radiotherapy (2D-CRT) in the treatment of patients with nasopharyngeal carcinoma (NPC). A retrospective review of data from 1,276 patients with biopsy-proven, nonmetastatic NPC was performed. All patients had undergone magnetic resonance imaging and were staged according to the sixth edition of the American Joint Committee on Cancer staging criteria. Radiotherapy was the primary treatment for all patients. Of the 1,276 patients, 512 were treated with IMRT and 764 with 2D-CRT. The 5-year actuarial local relapse-free survival (LRFS), the nodal relapse-free survival (NRFS), the distant metastasis-free survival (DMFS), and the disease-free survival (DFS) rates were 92.7%, 97.0%, 84.0%, and 75.9%, respectively, for the IMRT group, and 86.8%, 95.5%, 82.6%, and 71.4%, respectively, for the 2D-CRT group. In stage T1 patients, improvement of LRFS in the IMRT group was even significantly higher than in the 2D-CRT group (100% vs. 94.4%; p = 0.016). A trend of improvement of DFS was observed in the IMRT group compared with the 2D-CRT group but without reaching statistical significance. NRFS and DMFS rates were similar in the two groups. A greater improvement of treatment results with IMRT than with 2D-CRT was demonstrated primarily by achieving a higher local tumor control rate in NPC patients, especially in the early T stage patients. The goal of better control of both local failure in advanced, nonmetastatic NPC patients and of distant failure should be addressed in future studies. Copyright © 2011 Elsevier Inc. All rights reserved.
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              Upregulation of miRNA-155 promotes tumour angiogenesis by targeting VHL and is associated with poor prognosis and triple-negative breast cancer

              MicroRNA-155 (miR-155) is frequently up-regulated in various types of human cancer; however, its role in cancer angiogenesis remains unknown. Here, we demonstrate the role of miR-155 in angiogenesis through targeting von Hippel-Lindau tumour suppressor (VHL) in breast cancer. Ectopic expression of miR-155 induced whereas knockdown of miR-155 inhibited HUVEC network formation, proliferation, invasion, and migration. Furthermore, mammary fat pad xenotransplantation of ectopically expressed miR-155 resulted in extensive angiogenesis, proliferation, tumour necrosis, and recruitment of pro-inflammatory cells such as tumour associated macrophages. Expression of VHL abrogated these miR-155 effects. Moreover, miR-155 expression inversely correlates with VHL expression level and is associated with late stage, lymph node metastasis, and poor prognosis as well as triple-negative tumour in breast cancer. These findings indicate that miR-155 plays a pivotal role in tumour angiogenesis by downregulation of VHL, and provide a basis for miR-155-expressing tumours to embody an aggressive malignant phenotype, and therefore, miR-155 is an important therapeutic target in breast cancer.
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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 2015
                19 January 2015
                19 January 2015
                : 11
                : 5
                : 3330-3336
                Affiliations
                Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
                Author notes
                Correspondence to: Professor Yawei Yuan, Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Great Road, Guangzhou, Guangdong 510515, P.R. China, E-mail: yuanyw66@ 123456aliyun.com
                [*]

                Contributed equally

                Article
                mmr-11-05-3330
                10.3892/mmr.2015.3221
                4368084
                25607713
                b7bd3d40-1037-430b-89af-702e45fd90c1
                Copyright © 2015, Spandidos Publications

                This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

                History
                : 14 April 2014
                : 06 August 2014
                Categories
                Articles

                microrna,nasopharyngeal carcinoma,radioresistance,mir-101,stathmin 1

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