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Expression of somatostatin receptor subtype 2 in growth hormone-secreting pituitary adenoma and the regulation of miR-185

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Abstract

Introduction

Long-acting somatostatin analogs (SSAs) are most widely used to treat growth hormone (GH)-secreting pituitary adenoma. However, approximately 30 % of treated patients show resistance to SSAs, which may be associated with the reduction of somatostatin receptor subtype 2 (SSTR2) mRNA and protein expression.

Materials and methods

The present study used immunohistochemistry to detect the expression of SSTR2 and SSTR5 in twenty human GH-secreting adenoma samples treated with SSAs and seven normal pituitary samples.

Results

The staining intensities of SSTR2 and SSTR5 were stronger in most adenoma samples than in normal pituitary. The expression of SSTR2 tended to be lower in the SSA non-responder group than in responders. A search of the Bioinformatics data bank and the miRCURY™ LNA array confirmed miR-185 as the putative mircoRNA (miRNA) regulating the expression of SSTR2. An in vitro study using Dual Luciferase reporter assay demonstrated that miR-185 likely targets the 3′-UTR of SSTR2 mRNA in the rat pituitary adenoma GH3 cell line. MiR-185 also downregulated or upregulated the expression of SSTR2 mRNA and SSTR2 protein, following transfection with miR-185 mimics or inhibitors, respectively.

Conclusion

MiR-185 enhanced the cell proliferation and inhibited the apoptosis of GH3 cells.

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Abbreviations

SSA:

Somatostatin analogs

SSTR:

Somatostatin receptor subtype

GH:

Growth hormone

IGF-I:

Insulin-like growth factor I

SRIF:

Somatostatin release-inhibiting factors

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Acknowledgments

This research was supported by the National Natural Science Foundation of China (No. 41076092, 30971538), the Guangdong Provincial 125 Key Laboratory Foundation of Medicine (K970401302), Science and Technology Foundation of Guangzhou (2013J4100055), and the Science and Technology Foundation of Zhuhai (2014D0401990011).

Conflict of interest

The authors report no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Review Board of the First Affiliated Hospital, Sun Yat-sen University and of the local ethics committee, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Tissue samples were collected in accordance with the guidelines of local committee on human research. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study and all participants provided informed written consent.

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Authors and Affiliations

  1. Department of Neurosurgery and Pituitary Tumor Center, Zhongshan School of Medicine, The First Affiliated Hospital of Sun Yat-sen University, 52# Zhongshan Er Road, Guangzhou, 510080, China

    X. Fan, Z. Mao, D. He, C. Liao, X. Jiang, B. Hu & H. Wang

  2. Department of Neurosurgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, China

    X. Fan

  3. Department of Histology and Embryology, Medical school of Sun Yat-sen University, 74# Zhongshan Er Road, Guangzhou, 510080, China

    N. Lei, X. Wang & Y. Zhu

  4. Department of Pathology, The First Affiliated hospital of Sun Yat-sen University, Guangzhou, 510080, China

    Z. Li

  5. Department of Pathology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, China

    Y. Lin & X. Gou

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  1. X. Fan
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Correspondence to Y. Zhu or H. Wang.

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Fan, X., Mao, Z., He, D. et al. Expression of somatostatin receptor subtype 2 in growth hormone-secreting pituitary adenoma and the regulation of miR-185. J Endocrinol Invest 38, 1117–1128 (2015). https://doi.org/10.1007/s40618-015-0306-7

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  • DOI: https://doi.org/10.1007/s40618-015-0306-7

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