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MicroRNA involvement in a metastatic non-functioning pituitary carcinoma

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Abstract

Purpose

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.

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Acknowledgments

We thank Dr. Shijuan Gao (Institute of Microbiology, Chinese Academy of Sciences, Beijing, China) for her advice on this work. This work was supported by the National Natural Science Foundation of China (No. 81072084 and No. 81372414) and Beijing capital development fund (No. 2011400106).

Conflict of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Research involving human participants

The protocol collecting primary pituitary tumors was approved by the Institutional Review Board at the Wuhan General Hospital (Wuhan, China); the protocol harvesting the metastatic lesion and other pituitary tumor specimens was approved by the Institutional Review Board at the Peking Union Medical College Hospital (Beijing, China).

Informed consent

Informed consent was obtained from each individual patient at the Wuhan General Hospital and the Peking Union Medical College Hospital.

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    Authors and Affiliations

    1. Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China

      Zhenqing Wei, Yong Yao, Wenbin Ma & Renzhi Wang

    2. Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA

      Cuiqi Zhou

    3. Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China

      Mei Liu

    4. Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China

      Jian Sun

    5. Department of Neurosurgery, The First Hospital of Qiqihar, Qiqihar, Heilongjiang Province, People’s Republic of China

      Jianqi Xiao

    6. Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China

      Huijuan Zhu

    7. Department of Neurosurgery, The First Hospital Affiliated to Dalian Medical University, Dalian, Liaoning Province, People’s Republic of China

      Zhenqing Wei

    8. Joint Pituitary Research Center of CSMC & PUMCH, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China

      Cuiqi Zhou & Renzhi Wang

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    1. Zhenqing Wei
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    Correspondence to Huijuan Zhu or Renzhi Wang.

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    Zhengqing Wei and Cuiqi Zhou have contributed equally to this publication.

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    Wei, Z., Zhou, C., Liu, M. et al. MicroRNA involvement in a metastatic non-functioning pituitary carcinoma. Pituitary 18, 710–721 (2015). https://doi.org/10.1007/s11102-015-0648-3

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