X Fan1,2, Z Mao1, D He1, C Liao1, X Jiang1, N Lei3, B Hu1, X Wang3, Z Li4, Y Lin5, X Gou5, Y Zhu6, H Wang7. 1. Department of Neurosurgery and Pituitary Tumor Center, Zhongshan School of Medicine, The First Affiliated Hospital of Sun Yat-sen University, 52# Zhongshan Er Road, Guangzhou, 510080, China. 2. Department of Neurosurgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, China. 3. Department of Histology and Embryology, Medical school of Sun Yat-sen University, 74# Zhongshan Er Road, Guangzhou, 510080, China. 4. Department of Pathology, The First Affiliated hospital of Sun Yat-sen University, Guangzhou, 510080, China. 5. Department of Pathology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, China. 6. Department of Histology and Embryology, Medical school of Sun Yat-sen University, 74# Zhongshan Er Road, Guangzhou, 510080, China. Zhuyongh@mail.sysu.edu.cn. 7. Department of Neurosurgery and Pituitary Tumor Center, Zhongshan School of Medicine, The First Affiliated Hospital of Sun Yat-sen University, 52# Zhongshan Er Road, Guangzhou, 510080, China. Wanghaij@mail.sysu.edu.cn.
Abstract
INTRODUCTION: Long-acting somatostatin analogs (SSAs) are most widely used to treat growth hormone (GH)-secreting pituitary adenoma. However, approximately 30 % of treated patients show resistance to SSAs, which may be associated with the reduction of somatostatin receptor subtype 2 (SSTR2) mRNA and protein expression. MATERIALS AND METHODS: The present study used immunohistochemistry to detect the expression of SSTR2 and SSTR5 in twenty human GH-secreting adenoma samples treated with SSAs and seven normal pituitary samples. RESULTS: The staining intensities of SSTR2 and SSTR5 were stronger in most adenoma samples than in normal pituitary. The expression of SSTR2 tended to be lower in the SSA non-responder group than in responders. A search of the Bioinformatics data bank and the miRCURY™ LNA array confirmed miR-185 as the putative mircoRNA (miRNA) regulating the expression of SSTR2. An in vitro study using Dual Luciferase reporter assay demonstrated that miR-185 likely targets the 3'-UTR of SSTR2 mRNA in the rat pituitary adenoma GH3 cell line. MiR-185 also downregulated or upregulated the expression of SSTR2 mRNA and SSTR2 protein, following transfection with miR-185 mimics or inhibitors, respectively. CONCLUSION: MiR-185 enhanced the cell proliferation and inhibited the apoptosis of GH3 cells.
INTRODUCTION: Long-acting somatostatin analogs (SSAs) are most widely used to treat growth hormone (GH)-secreting pituitary adenoma. However, approximately 30 % of treated patients show resistance to SSAs, which may be associated with the reduction of somatostatin receptor subtype 2 (SSTR2) mRNA and protein expression. MATERIALS AND METHODS: The present study used immunohistochemistry to detect the expression of SSTR2 and SSTR5 in twenty human GH-secreting adenoma samples treated with SSAs and seven normal pituitary samples. RESULTS: The staining intensities of SSTR2 and SSTR5 were stronger in most adenoma samples than in normal pituitary. The expression of SSTR2 tended to be lower in the SSA non-responder group than in responders. A search of the Bioinformatics data bank and the miRCURY™ LNA array confirmed miR-185 as the putative mircoRNA (miRNA) regulating the expression of SSTR2. An in vitro study using Dual Luciferase reporter assay demonstrated that miR-185 likely targets the 3'-UTR of SSTR2 mRNA in the ratpituitary adenoma GH3 cell line. MiR-185 also downregulated or upregulated the expression of SSTR2 mRNA and SSTR2 protein, following transfection with miR-185 mimics or inhibitors, respectively. CONCLUSION:MiR-185 enhanced the cell proliferation and inhibited the apoptosis of GH3 cells.
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