Department of Neurosurgery and Pituitary Tumor Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Diagn Pathol. 2010 Dec 7;5:79. doi: 10.1186/1746-1596-5-79.
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).
Fifteen 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.
Fifty-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.
Our 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.
本研究旨在：（1）鉴定生长激素（GH）分泌性垂体腺瘤中特定的 miRNA；（2）确定这些 miRNA 的表达与肿瘤大小、生长抑素类似物治疗以及对生长抑素类似物（SSA）的反应之间的关系。
15 例 GH 分泌性腺瘤患者在手术前接受兰瑞肽治疗 4 个月。以兰瑞肽使 GH 分泌减少 50%的患者为 SSA 反应者，而 GH 减少少于 50%的患者为 SSA 无反应者。我们通过 miRCURY™ LNA 阵列分析了 21 例 GH 分泌性垂体腺瘤和 6 例正常垂体中的 miRNA，并用定量实时 PCR 验证了一些差异表达的 miRNA。
GH 分泌性垂体腺瘤与正常垂体之间有 52 个 miRNA 表达差异。微腺瘤和大腺瘤之间观察到 9 个 miRNA 的差异表达。兰瑞肽治疗组和未治疗组肿瘤样本之间有 13 个 miRNA 表达差异。SSA 反应者或 GH 无反应者之间有 7 个 miRNA 表达差异。一些鉴定出的 miRNA 可能参与细胞增殖、凋亡、癌症发生和进展。
我们的结果表明，miRNA 表达的改变参与了 GH 分泌性垂体腺瘤的转化，这将为 SSA 治疗肢端肥大症的机制提供启示。改变的 miRNA 基因的靶标的鉴定和表征可能阐明垂体腺瘤发病机制中涉及的分子机制。
