Differential expression of microRNAs in GH-secreting pituitary adenomas.
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.
Department of Neurosurgery and Pituitary Tumor Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Zhi-Gang
ZG
Mao
Dong-Sheng
DS
He
Jing
J
Zhou
Bin
B
Yao
Wei-Wei
WW
Xiao
Chun-Hua
CH
Chen
Yong-Hong
YH
Zhu
Hai-Jun
HJ
Wang
D000236:Adenoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D016000:Cluster Analysis; D020869:Gene Expression Profiling / Q000379:methods; D005838:Genotype; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D006801:Humans; D035683:MicroRNAs / Q000032:analysis*; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D010456:Peptides, Cyclic / Q000627:therapeutic use; D010641:Phenotype; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000031:analogs & derivatives / Q000627:therapeutic use; D047368:Tumor Burden
D018931:Antineoplastic Agents, Hormonal; D035683:MicroRNAs; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin