title: MicroRNA involvement in a metastatic non-functioning pituitary carcinoma.
abstract: OBJECTIVE
  Pituitary carcinomas are extremely rare neoplasms, and molecular events leading to malignant pituitary transformation are largely unknown. Enhanced understanding of molecular mechanisms driving malignant pituitary progression would be beneficial for pituitary carcinoma diagnosis and treatment.
  
  
  METHODS
  Differential microRNA expression in paired primary and metastatic pituitary carcinoma specimens were detected using high-throughput human microRNA microarrays and TaqMan microRNA arrays. Three of significantly deregulated miRNAs were further confirmed using quantitative real-time PCR in the metastatic carcinoma, six atypical pituitary adenomas and eight typical pituitary adenomas. Target genes of microRNAs were bioinformatically predicated and verified in vitro by Western blotting and real-time PCR and in vivo by immunohistochemistry respectively.
  
  
  RESULTS
  We present a case of a 50-year-old woman harboring non-functioning pituitary carcinoma with multiple intracranial metastases, and identified up-regulation of miR-20a, miR-106b and miR-17-5p in the metastatic carcinoma as compared to the primary neoplasm. Furthermore, miR-20a and miR-17-5p were increased in the metastatic carcinoma and six atypical pituitary adenomas as compared to eight typical pituitary adenomas as measured by quantitative real-time PCR. Both PTEN and TIMP2 were bioinformatically predicated and confirmed in vitro as target genes of these three microRNAs. As semi-quantified by immunohistochemistry, PTEN was absent and TIMP2 was decreased in the metastatic pituitary carcinoma as compared to pituitary adenomas.
  
  
  CONCLUSIONS
  Our results suggest microRNA involvement in malignant pituitary progression, whereby increased miR-20a, miR-106b and miR-17-5p promote metastasis by attenuating PTEN and TIMP2 in pituitary carcinoma.
authors: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People's Republic of China.
authors: Zhenqing
authors: Z
authors: Wei
authors: Cuiqi
authors: C
authors: Zhou
authors: Mei
authors: M
authors: Liu
authors: Yong
authors: Y
authors: Yao
authors: Jian
authors: J
authors: Sun
authors: Jianqi
authors: J
authors: Xiao
authors: Wenbin
authors: W
authors: Ma
authors: Huijuan
authors: H
authors: Zhu
authors: Renzhi
authors: R
authors: Wang
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000556:secondary / Q000601:surgery; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008279:Magnetic Resonance Imaging; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; C542541:MIRN106 microRNA, human; C524941:MIRN17 microRNA, human; C534451:MIRN20a microRNA, human; D035683:MicroRNAs; C560823:TIMP2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human