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.
Keywords: GH-secreting pituitary adenoma; MicroRNA-185; Somatostatin analog; Somatostatin receptor subtype 2.