Fei Zeng1, Min Xue2, Ting Xiao3, Yueran Li1, Songshu Xiao1, Bin Jiang1, Caiping Ren4. 1. Department of Gynecology, the Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China. 2. Department of Gynecology, the Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China. Electronic address: xumin_gyn@163.com. 3. Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China. 4. Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, School of Basic Medical Science, Central South University, Xiangya Road 110, Changsha 410078, Hunan Province, China. Electronic address: rencaiping@csu.edu.cn.
Abstract
BACKGROUND: Previous studies have revealed the important role of miR-200b in cancer biology, including its upregulation in cervical cancer. However, miR-200b function in cervical cancer progression remains unclear. Thus, this study aims to explore the functional role of miR-200b in cervical cancer development, involving its potential regulation on FoxG1, one transcriptional repressor. METHODS: Thirty paired cervical cancer samples were used to analyze the expression of miR-200b and FoxG1 by real time PCR and western blot analysis. Further gain- and loss-of-function studies were performed to validate FoxG1 as one miR-200b target, in line with luciferase report assays. MiR-200b silence was also conducted to observe its regulation on cell viability, migration and invasion in vitro, while tumor growth in vivo was tracked through the delivery of miR-200b inhibitor. RESULTS: MiR-200b upregulation was confirmed in cancer tissues or cells as compared to normal controls, while FoxG1 downregulation was observed and then FoxG1 was definitely validated as one miR-200b target. Further in vitro studies showed that enforced miR-200b downregulation induced the decrease of cell ability, with increased cell apoptosis, and attenuated ability of cell migration and invasion in both HeLa and C33A cells, while further inhibition of FoxG1 expression could reverse all these changes. In addition, miR-200b silence in vivo strongly inhibited tumor growth. CONCLUSION: Upregulated miR-200b in cervical cancer was proven to show positive regulation on cervical cancer development by directly targeting FoxG1. Moreover, miR-200b silence was proposed to inhibit tumor growth in vivo, implying its therapeutic value in cervical cancer treatment.
BACKGROUND: Previous studies have revealed the important role of miR-200b in cancer biology, including its upregulation in cervical cancer. However, miR-200b function in cervical cancer progression remains unclear. Thus, this study aims to explore the functional role of miR-200b in cervical cancer development, involving its potential regulation on FoxG1, one transcriptional repressor. METHODS: Thirty paired cervical cancer samples were used to analyze the expression of miR-200b and FoxG1 by real time PCR and western blot analysis. Further gain- and loss-of-function studies were performed to validate FoxG1 as one miR-200b target, in line with luciferase report assays. MiR-200b silence was also conducted to observe its regulation on cell viability, migration and invasion in vitro, while tumor growth in vivo was tracked through the delivery of miR-200b inhibitor. RESULTS:MiR-200b upregulation was confirmed in cancer tissues or cells as compared to normal controls, while FoxG1 downregulation was observed and then FoxG1 was definitely validated as one miR-200b target. Further in vitro studies showed that enforced miR-200b downregulation induced the decrease of cell ability, with increased cell apoptosis, and attenuated ability of cell migration and invasion in both HeLa and C33A cells, while further inhibition of FoxG1 expression could reverse all these changes. In addition, miR-200b silence in vivo strongly inhibited tumor growth. CONCLUSION: Upregulated miR-200b in cervical cancer was proven to show positive regulation on cervical cancer development by directly targeting FoxG1. Moreover, miR-200b silence was proposed to inhibit tumor growth in vivo, implying its therapeutic value in cervical cancer treatment.
Authors: Angelica Judith Granados-López; José Luis Ruiz-Carrillo; Luis Steven Servín-González; José Luis Martínez-Rodríguez; Claudia Araceli Reyes-Estrada; Rosalinda Gutiérrez-Hernández; Jesús Adrián López Journal: Int J Mol Sci Date: 2017-02-14 Impact factor: 5.923