Download PDF
Horm Metab Res 2017; 49(07): 550-557
DOI: 10.1055/s-0043-106437
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

MicroRNA-524-5p Functions as a Tumor Suppressor in a Human Pituitary Tumor-Derived Cell Line

Wang Zhen   *
1   Department of Histology and Embryology, Medical school of Sun Yat-sen University, Guangzhou, Guangdong, China
2   Key Laboratory of Functional Molecules from Marine Microorganisms, Department of Education of Guangdong Province, Sun Yat-sen University, Guangzhou, Guangdong, China
,
Du Qiu   *
1   Department of Histology and Embryology, Medical school of Sun Yat-sen University, Guangzhou, Guangdong, China
2   Key Laboratory of Functional Molecules from Marine Microorganisms, Department of Education of Guangdong Province, Sun Yat-sen University, Guangzhou, Guangdong, China
,
Chen Zhiyong
3   Department of Neurosurgery and Pituitary Tumour Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
,
Wang Xin
1   Department of Histology and Embryology, Medical school of Sun Yat-sen University, Guangzhou, Guangdong, China
2   Key Laboratory of Functional Molecules from Marine Microorganisms, Department of Education of Guangdong Province, Sun Yat-sen University, Guangzhou, Guangdong, China
,
Jian Mengyao
1   Department of Histology and Embryology, Medical school of Sun Yat-sen University, Guangzhou, Guangdong, China
2   Key Laboratory of Functional Molecules from Marine Microorganisms, Department of Education of Guangdong Province, Sun Yat-sen University, Guangzhou, Guangdong, China
,
Zhu Dimin
3   Department of Neurosurgery and Pituitary Tumour Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
,
Hu Chonghui
1   Department of Histology and Embryology, Medical school of Sun Yat-sen University, Guangzhou, Guangdong, China
2   Key Laboratory of Functional Molecules from Marine Microorganisms, Department of Education of Guangdong Province, Sun Yat-sen University, Guangzhou, Guangdong, China
,
Wang Haijun
3   Department of Neurosurgery and Pituitary Tumour Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
,
Zhu Yonghong
1   Department of Histology and Embryology, Medical school of Sun Yat-sen University, Guangzhou, Guangdong, China
2   Key Laboratory of Functional Molecules from Marine Microorganisms, Department of Education of Guangdong Province, Sun Yat-sen University, Guangzhou, Guangdong, China
› Author Affiliations
Further Information

Publication History

received 31 October 2016

accepted 08 March 2017

Publication Date:
04 May 2017 (online)

Also available at
    Permissions and Reprints

Abstract

Clinical nonfunctional pituitary adenomas (NFAs) account for about 40% of pituitary adenomas with almost no clinically relevant hormonal symptoms. Increasing evidence shows that many microRNAs are involved in the development and progression of pituitary adenomas. MicroRNA-524-5p (miR-524-5p) has been reported to cause characteristic alterations in various tumors. However, the functional importance of miR-524-5p in NFAs remains unknown. The aim of this study was to explore the effects of overexpressing miR-524-5p on the proliferation, migration, invasion, and tumorigenicity of pituitary-derived folliculostellate (PDFS) cells using lentiviral transfection. Interestingly, the results showed that overexpressing miR-524-5p downregulated pituitary tumor-transforming gene 1 (PTTG1) binding factor (PBF) expression at both mRNA and protein levels and significantly attenuated cell proliferation, clonogenicity, migration, and invasion in vitro. Moreover, enhancing miR-524-5p blocked tumor growth in a nude mouse xenograft model in vivo. These findings suggest that miR-524-5p appears to play a critical role in the regulation of biological properties of PDFS cells, and may represent a potential therapeutic target for NFAs.

Key words

microRNA - pituitary adenoma - PBF

* These authors contributed equally to this work


 

  • References

  • 1 Ezzat S, Asa SL, Couldwell WT, Barr CE, Dodge WE, Vance ML, McCutcheon IE. The prevalence of pituitary adenomas: A systematic review. Cancer 2004; 101: 613-619
    CrossrefPubMedGoogle Scholar
  • 2 Reddy R, Cudlip S, Byrne JV, Karavitaki N, Wass JAH. Can we ever stop imaging in surgically treated and radiotherapy-naive patients with non-functioning pituitary adenoma?. Eur J Endocrinol 2011; 165: 739-744
    CrossrefPubMedGoogle Scholar
  • 3 Evans CO, Halkar RK, Oyesiku NA. Clinically non-functional pituitary tumors: The surgical and biological challenge. In: Kanno T, Kato Y. (eds.) Minimally Invasive Neurosurgery and Multidisciplinary Neurotraumatology. Berlin: Springer; 2006: 8-16
    CrossrefGoogle Scholar
  • 4 Xekouki P, Azevedo M, Stratakis CA. Anterior pituitary adenomas: inherited syndromes, novel genes and molecular pathways. Expert Rev Endocrinol Metab 2010; 5: 697-709
    CrossrefPubMedGoogle Scholar
  • 5 Binse I, Ueberberg B, Sandalcioglu IE, Flitsch J, Luedecke DK, Mann K, Petersenn S. Expression analysis of GADD45gamma, MEG3, and p8 in pituitary adenomas. Horm Metab Res 2014; 46: 644-650
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Bartel DP. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 2004; 116: 281-297
    CrossrefPubMedGoogle Scholar
  • 7 Gadelha MR, Kasuki L, Denes J, Trivellin G, Korbonits M. MicroRNAs: Suggested role in pituitary adenoma pathogenesis. J Endocrinol Invest 2013; 36: 889-895
    CrossrefPubMedGoogle Scholar
  • 8 Liu GH, Liu YH, Yang Z, Zhu AL, Zhao CL. MicroRNA-524-5p suppresses the growth and invasive abilities of gastric cancer cells. Oncol Lett 2016; 11: 1926-1932
    CrossrefPubMedGoogle Scholar
  • 9 Chen L, Zhang W, Yan W, Han L, Zhang K, Shi Z, Zhang J, Wang Y, Li Y, Yu S, Pu P, Jiang C, Jiang T, Kang C. The putative tumor suppressor miR-524-5p directly targets Jagged-1 and Hes-1 in glioma. Carcinogenesis 2012; 33: 2276-2282
    CrossrefPubMedGoogle Scholar
  • 10 Liu SM, Lu J, Lee HC, Chung FH, Ma N. miR-524-5p suppresses the growth of oncogenic BRAF melanoma by targeting BRAF and ERK2. Oncotarget 2014; 5: 9444-9459
    CrossrefPubMedGoogle Scholar
  • 11 Mao ZG, He DS, Zhou J, Yao B, Xiao WW, Chen CH, Zhu YH, Wang HJ. Differential expression of microRNAs in GH-secreting pituitary adenomas. Diagn Pathol 2010; 5: 79
    CrossrefPubMedGoogle Scholar
  • 12 Danila DC, Zhang X, Zhou Y, Dickersin GR, Fletcher JA, Hedley-Whyte ET, Selig MK, Johnson SR, Klibanski A. A human pituitary tumor-derived folliculostellate cell line. J Clin Endocrinol Metab 2000; 85: 1180-1187
    PubMedGoogle Scholar
  • 13 McCabe CJ, Khaira JS, Boelaert K, Heaney AP, Tannahill LA, Hussain S, Mitchell R, Olliff J, Sheppard MC, Franklyn JA, Gittoes N. Expression of pituitary tumour transforming gene (PTTG) and fibroblast growth factor-2 (FGF-2) in human pituitary adenomas: Relationships to clinical tumour behaviour. Clin Endocrinol 2003; 58: 141-150
    CrossrefPubMedGoogle Scholar
  • 14 Chunharojrith P, Nakayama Y, Jiang X, Kery RE, Ma J, De La Hoz UC, Zhang X, Zhou Y, Klibanski A. Tumor suppression by MEG3 lncRNA in a human pituitary tumor derived cell line. Mol Cell Endocrinol 2015; 416: 27-35
    CrossrefPubMedGoogle Scholar
  • 15 Morand I, Fonlupt P, Guerier A, Trouillas J, Calle A, Remy C, Rousset B, Munari-Silem Y. Cell-to-cell communication in the anterior pituitary: Evidence for gap junction-mediated exchanges between endocrine cells and folliculostellate cells. Endocrinology 1996; 137: 3356-3367
    CrossrefPubMedGoogle Scholar
  • 16 Roncaroli F, Scheithauer BW, Cenacchi G, Horvath E, Kovacs K, Lloyd RV, Abell-Aleff P, Santi M, Yates AJ. ‘Spindle cell oncocytoma’ of the adenohypophysis: A tumor of folliculostellate cells?. Am J Surg Pathol 2002; 26: 1048-1055
    CrossrefPubMedGoogle Scholar
  • 17 Coire CI, Horvath E, Smyth HS, Kovacs K. Rapidly recurring folliculostellate cell tumor of the adenohypophysis with the morphology of a spindle cell oncocytoma: Case report with electron microscopic studies. Clin Neuropathol 2009; 28: 303-308
    CrossrefPubMedGoogle Scholar
  • 18 Hori S, Hayashi N, Fukuoka J, Kurimoto M, Hamada H, Miyajima K, Nagai S, Endo S. Folliculostellate cell tumor in pituitary gland. Neuropathology 2009; 29: 78-80
    CrossrefPubMedGoogle Scholar
  • 19 Li FQ, Xu B, Wu YJ, Yang ZL, Qian JJ. Differential microRNA expression in signet-ring cell carcinoma compared with tubular adenocarcinoma of human gastric cancer. Genet Mol Res 2015; 14: 739-747
    CrossrefPubMedGoogle Scholar
  • 20 Li Y, Xu J, Chen H, Bai J, Li S, Zhao Z, Shao T, Jiang T, Ren H, Kang C, Li X. Comprehensive analysis of the functional microRNA-mRNA regulatory network identifies miRNA signatures associated with glioma malignant progression. Nucl Acids Res 2013; 41
    PubMed
  • 21 Yaspo ML, Aaltonen J, Horelli-Kuitunen N, Peltonen L, Lehrach H. Cloning of a novel human putative type Ia integral membrane protein mapping to 21q22.3. Genomics 1998; 49: 130-136
    PubMedGoogle Scholar
  • 22 Stratford AL, Boelaert K, Tannahill LA, Kim DS, Warfield A, Eggo MC, Gittoes N, Young LS, Franklyn JA, McCabe CJ. Pituitary tumor transforming gene binding factor: A novel transforming gene in thyroid tumorigenesis. J Clin Endocrinol Metab 2005; 90: 4341-4349
    CrossrefPubMedGoogle Scholar
  • 23 Chien WW, Pei L. A novel binding factor facilitates nuclear translocation and transcriptional activation function of the pituitary tumor-transforming gene product. J Biol Chem 2000; 275: 19422-19427
    CrossrefPubMedGoogle Scholar
  • 24 Watkins RJ, Imruetaicharoenchoke W, Read ML, Sharma N, Poole VL, Gentillin E, Bansal S, Bosseboeuf E, Fletcher R, Nieto HR, Mallick U, Hackshaw A, Mehanna H, Boelaert K, Smith VE, McCabe CJ. Pro-invasive effect of proto-oncogene PBF is modulated by an interaction with cortactin. J Clin Endocrinol Metab 2016; c20161932
    PubMed
  • 25 Li C, Wang Y, Wang S, Wu B, Hao J, Fan H, Ju Y, Ding Y, Chen L, Chu X, Liu W, Ye X, Meng S. Hepatitis B Virus mRNA-Mediated miR-122 Inhibition Upregulates PTTG1-Binding Protein, Which Promotes Hepatocellular Carcinoma Tumor Growth and Cell Invasion. J Virol 2013; 87: 2193-2205
    CrossrefPubMedGoogle Scholar