Differential expression of microRNAs in GH-secreting pituitary adenomas

Zhi-Gang Mao, Dong-Sheng He, Jing Zhou, Bin Yao, Wei-Wei Xiao, Chun-Hua Chen, Yong-Hong Zhu, Hai-Jun Wang, Zhi-Gang Mao, Dong-Sheng He, Jing Zhou, Bin Yao, Wei-Wei Xiao, Chun-Hua Chen, Yong-Hong Zhu, Hai-Jun Wang

Abstract

Background: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

Trial registration: ClinicalTrials.gov NCT00993356.

Figures

Figure 1
Figure 1
Cluster analysis shows a clear distinction between GH-secreting pituitary adenomas and normal pituitary. GH-secreting pituitary adenomas: 1-21, Normal pituitary: 22-27.
Figure 2
Figure 2
Cluster analysis shows a clear distinction between macro- and microadenomas in GH-secreting pituitary adenomas. Macroadenomas:1-18, Microadenomas:19-21.
Figure 3
Figure 3
Cluster analysis shows a clear distinction between SSA Responders and SSA Noresponders in GH-secreting pituitary adenomas. SSA Responders:1-12, SSA Noresponders:13-15.

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