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      MiR-588 acts as an oncogene in ovarian cancer and increases the radioresistance of ovarian cancer cells

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          Abstract

          The therapeutic outcomes of ovarian cancer (OVCA) patients are majorly limited by the development of acquired chemo/radioresistance and the lack of targeted therapies. Accumulating studies demonstrate that microRNAs are involved in tumorigenesis and radioresistance. This study aims to illustrate the role of miR-588 in the radioresistance of OVCA cells. The levels of miR-588 and mRNAs were detected by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). OVCA cell viability, proliferative, migratory and invasive capacities were evaluated by the cell counting kit-8 (CCK-8) assay, colony formation assay, wound healing assay and transwell assay, respectively. The luciferase activities of plasmids containing wild -type and mutant serine/arginine-rich splicing factor 6 (SRSF6) 3'-untranslated region in miR-588 silenced OVCA cells were detected by a luciferase reporter assay. We found that miR-588 was overexpressed in OVCA tissues and cells. Knockdown of miR-588 exerted an inhibitory effect on the proliferation, migration and invasion and strengthened the radiosensitivity of OVCA cells, whereas overexpression of miR-588 increased the radioresistance of OVCA cells. SRSF6 was verified to be targeted by miR-588 in OVCA cells. In addition, the expression level of miR-588 was negatively correlated with that of SRSF6 in OVCA clinical samples. Rescue assays indicated that SRSF6 knockdown reversed the effect of miR-588 inhibition of OVCA cells under radiation. Overall, miR-588 acts as an oncogene in OVCA and increases the radioresistance of OVCA cells by targeting SRSF6.

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          Most cited references31

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          Ovarian cancer statistics, 2018

          In 2018, there will be approximately 22,240 new cases of ovarian cancer diagnosed and 14,070 ovarian cancer deaths in the United States. Herein, the American Cancer Society provides an overview of ovarian cancer occurrence based on incidence data from nationwide population-based cancer registries and mortality data from the National Center for Health Statistics. The status of early detection strategies is also reviewed. In the United States, the overall ovarian cancer incidence rate declined from 1985 (16.6 per 100,000) to 2014 (11.8 per 100,000) by 29% and the mortality rate declined between 1976 (10.0 per 100,000) and 2015 (6.7 per 100,000) by 33%. Ovarian cancer encompasses a heterogenous group of malignancies that vary in etiology, molecular biology, and numerous other characteristics. Ninety percent of ovarian cancers are epithelial, the most common being serous carcinoma, for which incidence is highest in non-Hispanic whites (NHWs) (5.2 per 100,000) and lowest in non-Hispanic blacks (NHBs) and Asians/Pacific Islanders (APIs) (3.4 per 100,000). Notably, however, APIs have the highest incidence of endometrioid and clear cell carcinomas, which occur at younger ages and help explain comparable epithelial cancer incidence for APIs and NHWs younger than 55 years. Most serous carcinomas are diagnosed at stage III (51%) or IV (29%), for which the 5-year cause-specific survival for patients diagnosed during 2007 through 2013 was 42% and 26%, respectively. For all stages of epithelial cancer combined, 5-year survival is highest in APIs (57%) and lowest in NHBs (35%), who have the lowest survival for almost every stage of diagnosis across cancer subtypes. Moreover, survival has plateaued in NHBs for decades despite increasing in NHWs, from 40% for cases diagnosed during 1992 through 1994 to 47% during 2007 through 2013. Progress in reducing ovarian cancer incidence and mortality can be accelerated by reducing racial disparities and furthering knowledge of etiology and tumorigenesis to facilitate strategies for prevention and early detection. CA Cancer J Clin 2018;68:284-296. © 2018 American Cancer Society.
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            Global cancer statistics in the year 2000.

            D Parkin (2001)
            Estimation of the burden of cancer in terms of incidence, mortality, and prevalence is a first step to appreciating appropriate control measures in a global context. The latest results of such an exercise, based on the most recent available international data, show that there were 10 million new cases, 6 million deaths, and 22 million people living with cancer in 2000. The most common cancers in terms of new cases were lung (1.2 million), breast (1.05 million), colorectal (945,000), stomach (876,000), and liver (564,000). The profile varies greatly in different populations, and the evidence suggests that this variation is mainly a consequence of different lifestyle and environmental factors, which should be amenable to preventive interventions. World population growth and ageing imply a progressive increase in the cancer burden--15 million new cases and 10 million new deaths are expected in 2020, even if current rates remain unchanged.
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              MicroRNA control of signal transduction.

              MicroRNAs (miRNAs) are integral elements in the post-transcriptional control of gene expression. After the identification of hundreds of miRNAs, the challenge is now to understand their specific biological function. Signalling pathways are ideal candidates for miRNA-mediated regulation owing to the sharp dose-sensitive nature of their effects. Indeed, emerging evidence suggests that miRNAs affect the responsiveness of cells to signalling molecules such as transforming growth factor-beta, WNT, Notch and epidermal growth factor. As such, miRNAs serve as nodes of signalling networks that ensure homeostasis and regulate cancer, metastasis, fibrosis and stem cell biology.
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                Author and article information

                Contributors
                Journal
                J Radiat Res
                J Radiat Res
                jrr
                Journal of Radiation Research
                Oxford University Press
                0449-3060
                1349-9157
                May 2023
                06 May 2023
                06 May 2023
                : 64
                : 3
                : 558-568
                Affiliations
                Department of Radiology, The Second Affiliated Hospital of Soochow University , No. 1055, Sanxiang Road, Gusu District, Suzhou, Jiangsu 215004, China
                Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University , No. 1055, Sanxiang Road, Gusu District, Suzhou, Jiangsu 215004, China
                Department of Radiology, The Second Affiliated Hospital of Soochow University , No. 1055, Sanxiang Road, Gusu District, Suzhou, Jiangsu 215004, China
                State Key Laboratory of Radiation Medicine and Protection, Soochow University , 199 Renai Road, Suzhou Industrial Park, Suzhou, Jiangsu 215123, China
                Department of Radiology, The Second Affiliated Hospital of Soochow University , No. 1055, Sanxiang Road, Gusu District, Suzhou, Jiangsu 215004, China
                Author notes
                Corresponding author. The Second Affiliated Hospital of Soochow University, No. 1055, Sanxiang Road, Gusu District, Suzhou, Jiangsu 215004, China. Email: panshiwen_88@ 123456126.com

                Xiaojuan Sua and Binbin Wang contributed equally to this work.

                Article
                rrad033
                10.1093/jrr/rrad033
                10214998
                37154623
                0751ce7c-a224-4e91-a52e-af21a8cd07e7
                © The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 12 January 2023
                : 5 March 2023
                : 28 March 2023
                Page count
                Pages: 11
                Funding
                Funded by: Social Development Guiding Program of Suzhou City in China;
                Award ID: SYSD2019110
                Funded by: Project of State Key Laboratory of Radiation Medicine and Protection, Soochow University;
                Award ID: GZK1202009
                Categories
                Regular paper
                Fundamental Radiation Science
                AcademicSubjects/MED00870
                AcademicSubjects/SCI00960

                Oncology & Radiotherapy
                ovarian cancer,radioresistance,mir-588,srsf6
                Oncology & Radiotherapy
                ovarian cancer, radioresistance, mir-588, srsf6

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