Jiayi Zhang1, Hengcheng Zhang1, Yuan Qin2, Chen Chen1, Jie Yang1, Ninghong Song1, Min Gu1. 1. Department of Urology, the First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China. 2. Department of Urology, Jiangsu Provincial Second Chinese Medicine Hospital, the Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210017, China.
Abstract
BACKGROUND: The microRNA (miRNA) miR-200c-3p is involved in the tumorigenesis and progression of a variety of cancers. However, the underlying regulatory role of miR-200c-3p in prostate cancer (PCa) remains unclear. METHODS: Online databases including Oncomine, Linkedomics and StarBase were used to investigate the clinical significance of miR-200c-3p, along with associated gene targets. PCa tissues and adjacent normal tissues were used for the detection of miR-200c-3p expression. A lentivirus overexpressing miR-200c-3p was constructed and transfected into PC3 and DU145 cells. Cell formation of proliferation, migration, and invasion were determined by cell viability and colony-formation assay, wound healing assay, and Matrigel invasion assay, respectively. Epithelial-mesenchymal transition (EMT)-associated markers were determined by qRT-PCR and Western blot. A luciferase reporter assay was performed to determine the direct relationship of miR-200c-3p and ZEB2. The tumor-suppressive role of miR-200c-3p was further confirmed by a xenograft tumor model and immunohistochemical (IHC) staining. RESULTS: Online database analyses showed that miR-200c-3p was associated with pathologic T and N stage in PCa, and miR-200c-3p was downregulated in PCa tissues. Overexpression of miR-200c-3p was considered a tumor suppressor and was found to significantly suppress the formation of migration and invasion in PCa cells via repression of E-cadherin-induced EMT. The bioinformatic database indicated that ZEB2 has a significant correlation with miR-200c-3p and was upregulated in PCa tissues. Further, ZEB2 expression was suppressed by the upregulation of miR-200c-3p and was identified as a direct target of miR-200c-3p. In addition, repression of ZEB2 could restore the levels of miR-200c-3p in PCa cells in turn, suggesting a potential negative loop between miR-200c-3p and ZEB2. miR-200c-3p also had an antitumor effect by negatively regulating ZEB2 in a xenograft mouse model. CONCLUSIONS: Taken together, the results of our study demonstrated the novel regulatory loop of miR-200c-3/ZEB2 in PCa progression, providing effective therapeutic strategies for PCa in the future.
BACKGROUND: The microRNA (miRNA) miR-200c-3p is involved in the tumorigenesis and progression of a variety of cancers. However, the underlying regulatory role of miR-200c-3p in prostate cancer (PCa) remains unclear. METHODS: Online databases including Oncomine, Linkedomics and StarBase were used to investigate the clinical significance of miR-200c-3p, along with associated gene targets. PCa tissues and adjacent normal tissues were used for the detection of miR-200c-3p expression. A lentivirus overexpressing miR-200c-3p was constructed and transfected into PC3 and DU145 cells. Cell formation of proliferation, migration, and invasion were determined by cell viability and colony-formation assay, wound healing assay, and Matrigel invasion assay, respectively. Epithelial-mesenchymal transition (EMT)-associated markers were determined by qRT-PCR and Western blot. A luciferase reporter assay was performed to determine the direct relationship of miR-200c-3p and ZEB2. The tumor-suppressive role of miR-200c-3p was further confirmed by a xenograft tumor model and immunohistochemical (IHC) staining. RESULTS: Online database analyses showed that miR-200c-3p was associated with pathologic T and N stage in PCa, and miR-200c-3p was downregulated in PCa tissues. Overexpression of miR-200c-3p was considered a tumor suppressor and was found to significantly suppress the formation of migration and invasion in PCa cells via repression of E-cadherin-induced EMT. The bioinformatic database indicated that ZEB2 has a significant correlation with miR-200c-3p and was upregulated in PCa tissues. Further, ZEB2 expression was suppressed by the upregulation of miR-200c-3p and was identified as a direct target of miR-200c-3p. In addition, repression of ZEB2 could restore the levels of miR-200c-3p in PCa cells in turn, suggesting a potential negative loop between miR-200c-3p and ZEB2. miR-200c-3p also had an antitumor effect by negatively regulating ZEB2 in a xenograft mouse model. CONCLUSIONS: Taken together, the results of our study demonstrated the novel regulatory loop of miR-200c-3/ZEB2 in PCa progression, providing effective therapeutic strategies for PCa in the future.
Authors: Tisheeka R Graham; Haiyen E Zhau; Valerie A Odero-Marah; Adeboye O Osunkoya; K Sean Kimbro; Mourad Tighiouart; Tongrui Liu; Jonathan W Simons; Ruth M O'Regan Journal: Cancer Res Date: 2008-04-01 Impact factor: 12.701
Authors: Sohail F Tavazoie; Claudio Alarcón; Thordur Oskarsson; David Padua; Qiongqing Wang; Paula D Bos; William L Gerald; Joan Massagué Journal: Nature Date: 2008-01-10 Impact factor: 49.962
Authors: Lukas Vrba; Taylor J Jensen; James C Garbe; Ronald L Heimark; Anne E Cress; Sally Dickinson; Martha R Stampfer; Bernard W Futscher Journal: PLoS One Date: 2010-01-13 Impact factor: 3.240