Abstract
BackgroundThe purpose of this study was to (1) identify specific miRNAs in growth hormones (GH)-secreting pituitary adenomas; (2) determine the relationship between the expression of these miRNAs and tumor size, somatostatin analogs treatment, and responsiveness to somatostatin analogs (SSA).MethodsFifteen GH-secreting adenomas patients were treated with lanreotide for 4 months before surgery. Patients with 50% reduction of GH secretion by lanreotide were considered as SSA responders, while patients with less than 50% of GH reduction were considered as SSA nonresponders. We analyzed the miRNAs in 21 GH-secreting pituitary adenomas and 6 normal pituitaries by miRCURY™ LNA array and some differentially expressed miRNAs were validated by quantitative real-time PCR.ResultsFifty-two miRNAs were differentially expressed between GH-secreting pituitary adenomas and normal pituitaries. Differential expression of 9 miRNAs was observed between micro- and macro-adenomas. Thirteen miRNAs were differentially expressed between tumor samples from lanreotide-treated patients and those from lanreotide-untreated patients. Seven miRNAs were differentially expressed between SSA responders or GH nonresponders. Several identified miRNAs may be involved in cell proliferation, apoptosis, cancer development and progression.ConclusionsOur results indicate that altered miRNAs expression is involved in GH-secreting pituitary adenomas transformation, which will shed light on the mechanisms for the treatment of acromegaly by SSA. Identification and characterization of the targets of altered miRNAs genes may elucidate molecular mechanisms involved in the pathogenesis of pituitary adenoma.
Highlights
The purpose of this study was to (1) identify specific miRNAs in growth hormones (GH)-secreting pituitary adenomas; (2) determine the relationship between the expression of these miRNAs and tumor size, somatostatin analogs treatment, and responsiveness to somatostatin analogs (SSA)
The biological diagnosis of acromegaly was based on the criteria that (1) plasma GH concentration is higher than 1 μg/l after oral administration of 75 g of glucose; (2) insulin-like growth factor 1 (IGF-1) concentration is increased compared to the normal population in the same age and sex; and (3) relevant clinical features associated with acromegaly occurred and pituitary adenoma appeared on the magnetic resonance imaging examination
The diagnosis of GH-secreting pituitary adenoma was confirmed by hematoxylin eosin (H&E) and immunohistochemical staining for all the samples (Additional file 2: Figure 1)
Summary
The purpose of this study was to (1) identify specific miRNAs in growth hormones (GH)-secreting pituitary adenomas; (2) determine the relationship between the expression of these miRNAs and tumor size, somatostatin analogs treatment, and responsiveness to somatostatin analogs (SSA). MiRNAs are a huge class of negative gene regulators controlling a wide range of biological functions such as cell proliferation, differentiation, miRNAs expression may be involved in pituitary tumorigenesis [11,12]. The role of transcriptional regulation of miRNAs and their target genes in the pathogenesis of pituitary adenomas remains largely unknown. A cascade of transcription factors and genetic elements normally determine the ability of somatotroph cells to synthesize and secrete growth hormone [13]. The possible role of these identified miRNAs was discussed
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