MicroRNAs and Target Genes in Pituitary Adenomas

AbstractPituitary adenomas account for the top three primary intracranial tumors in terms of total incidence rates. The clinical symptoms presented by the disease are often characterized by a series of systemic endocrine disorders, severe occupational lesions, and even some malignant features, and therefore early diagnosis and predicting recurrence would be instructive for clinical treatment of pituitary adenomas. An increasing number of specific microRNA (miRNA) expression signatures have been identified in pituitary, and miRNAs are related with the pituitary tumorigenesis, dysfunction, neurodegeneration, and metastatic non-functioning pituitary carcinoma. Here, this paper reviews the effects of aberrant miRNA expression in human pituitary adenomas and summarizes some corresponding target genes and biological significance over the last 7 years (2010–2017).

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MiR-148b, MiR-152/ALCAM Axis Regulates the Proliferation and Invasion of Pituitary Adenomas Cells

Cellular Physiology and Biochemistry ◽

10.1159/000485342 ◽

2017 ◽

Vol 44 (2) ◽

pp. 792-803 ◽

Cited By ~ 13

Author(s):

Wei He ◽

Ling Huang ◽

Min Li ◽

Yue Yang ◽

Zhen Chen ◽

...

Keyword(s):

Pituitary Adenomas ◽

Target Genes ◽

Annexin V ◽

Expression Level ◽

Human Pituitary ◽

Aberrant Expression ◽

Leukocyte Antigen ◽

Noninvasive Samples ◽

Proliferation And Invasion

Background/Aims: Aberrant expression of miRNA has been found in many tumor tissues to regulate the tumorigenesis by binding to the 3`- untranslated region (3`-UTR) of the target genes. The aim of this study is to investigate the role of miR-148b, miR-152/ALCAM axis in human pituitary adenomas (PAs). Methods: First, we detected the expression level of miR-148b-3p and miR-152 in human PAs samples by using qRT-PCR. Then we studied the role of miR-148b-3p, miR-152 on human PAs cell proliferation, invasion and apoptosis by using MTS assay, Transwell invasion assay and Annexin V/PI Staining Test. To study the relationship between miR-148b-3p, miR-152 and activated leukocyte antigen molecule (ALCAM), we overexpressed miR-148-3p or miR-152 by transfecting specific mimics. Lucifearase reporter assay was then performed to confirm the target. Next, we studied the biological functions of ALCAM in human PAs cells. Finally, the role of miR-148b-3p, miR-152/ALCAM axis in PAs cells was studied. Results: The expression level of miR-148-3p and miR-152 in invasive PAs samples was lower than those in noninvasive samples. Overexpression of miR-148b-3p, miR-152 could repress proliferation and invasion, and promote apoptosis. Moreover, miR-148b-3p and miR-152 could repress activated leukocyte antigen molecule (ALCAM) expression. Knockdown of ALCAM could repress proliferation and invasion and promote apoptosis. By contrary, overexpression of ALCAM promoted proliferation and invasion. Further, the rescue experiments indicated that overexpression of ALCAM significantly restored the proliferation, apoptosis, and invasion influenced by miR-148b-3p and miR-152. Conclusions: Our study suggests that miR-148b-3p, miR-152 may serve as suppressors in PAs through downregulating ALCAM expression. miR-148b, miR-152/ ALCAM axis may be a new therapeutic target in the future.

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Expression of Pit-1 and related proteins in diverse human pituitary adenomas

Journal of Molecular Endocrinology ◽

10.1677/jme.0.0110283 ◽

1993 ◽

Vol 11 (3) ◽

pp. 283-290 ◽

Cited By ~ 9

Author(s):

N Hoggard ◽

K Callaghan ◽

A Levy ◽

J R E Davis

Keyword(s):

Dna Binding ◽

Pituitary Adenomas ◽

Target Genes ◽

Gene Promoter ◽

Specific Protein ◽

Binding Activity ◽

Mobility Shift ◽

Human Pituitary ◽

Dna Binding Activity ◽

Human Pituitary Adenomas

ABSTRACT Pit-1, a member of the POU family of homeodomain transcription factors, activates prolactin and GH gene expression but also has a role in pituitary cell differentiation and proliferation. Expression of Pit-1 may therefore be of central importance in the function and phenotype of human pituitary adenomas. We have found evidence that, in addition to Pit-1 mRNA, Pit-1-like immunoreactivity and DNA-binding activity are readily detectable in a series of human pituitary adenomas. Gel mobility shift assays using adenoma protein extracts with two Pit-1-binding sites from the human prolactin gene promoter demonstrated the formation of several DNA sequence-specific protein—DNA complexes; some of these could be accounted for by Oct-1-binding activity. Pit-1 activity was anticipated in prolactin- and GH-secreting adenomas, but was also detected in a proportion of endocrine-inactive (non-secreting) adenomas that did not express Pit-1 target genes. The data demonstrate the presence of Pit-1 in a range of pituitary adenomas. Different adenomas generated slightly differing patterns of DNA-binding activity, though Pit-1 mRNA and protein size appeared normal in all tumours so far examined.

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PIT1 upregulation by HMGA proteins has a role in pituitary tumorigenesis

Endocrine Related Cancer ◽

10.1530/erc-11-0135 ◽

2011 ◽

Vol 19 (2) ◽

pp. 123-135 ◽

Cited By ~ 22

Author(s):

Dario Palmieri ◽

Teresa Valentino ◽

Ivana De Martino ◽

Francesco Esposito ◽

Paolo Cappabianca ◽

...

Keyword(s):

Pituitary Adenomas ◽

Gene Promoter ◽

Pituitary Tumour ◽

Human Pituitary ◽

Expression Levels ◽

Pituitary Tumorigenesis ◽

Its Gene ◽

Gland Development

We have previously demonstrated that HMGA1B and HMGA2 overexpression in mice induces the development of GH and prolactin (PRL) pituitary adenomas mainly by increasing E2F1 transcriptional activity. Interestingly, these adenomas showed very high expression levels of PIT1, a transcriptional factor that regulates the gene expression ofGh,Prl,GhrhrandPit1itself, playing a key role in pituitary gland development and physiology. Therefore, the aim of our study was to identify the role ofPit1overexpression in pituitary tumour development induced by HMGA1B and HMGA2. First, we demonstrated that HMGA1B and HMGA2 directly interact with both PIT1 and its gene promoterin vivo, and that these proteins positively regulatePit1promoter activity, also co-operating with PIT1 itself. Subsequently, we showed, by colony-forming assays on two different pituitary adenoma cell lines, GH3 and αT3, thatPit1overexpression increases pituitary cell proliferation. Finally, the expression analysis ofHMGA1,HMGA2andPIT1in human pituitary adenomas of different histological types revealed a direct correlation betweenPIT1and HMGA expression levels. Taken together, our data indicate a role ofPit1upregulation by HMGA proteins in pituitary tumours.

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The Involvement of miRNAs in Pituitary Adenomas Pathogenesis and the Clinical Implications

European Neurology ◽

10.1159/000521388 ◽

2022 ◽

pp. 1-6

Author(s):

Dingkai Xu ◽

Ling Wang

Keyword(s):

Pituitary Adenomas ◽

Malignant Tumors ◽

Tissue Level ◽

Clinical Implications ◽

Endocrine Disorders ◽

Intracranial Tumors ◽

Invasion And Metastasis ◽

Regulate Gene Expression ◽

Physiological Processes ◽

Total Incidence

Pituitary adenomas (PAs) account for the top three primary intracranial tumors in terms of total incidence rate. PAs can cause severe endocrine disorders and even malignant features, such as invasion, metastasis, and recurrence. Therefore, the early diagnosis and accurate prognosis would be greatly beneficial for clinical treatment of PAs. MicroRNAs (miRNAs) are small, protein-noncoding RNAs that regulate gene expression posttranscriptionally. They regulate essential physiological processes, including proliferation, growth, and apoptosis, and also they involve in the invasion and metastasis of malignant tumors. At the tissue level, differential miRNA expression in endocrine malignancies including PAs has been reported. When miRNAs have been successfully detected in various biofluids and cell-free environments, their important roles as potential screening or prognostic biomarkers have been extensively investigated. The current work reviews recent studies on the emerging roles of miRNAs in PAs and the clinical significance.

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Fine Structural Classification of Chromophobe Adenomas of the Human Pituitary Gland

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100115511 ◽

1975 ◽

Vol 33 ◽

pp. 378-379

Author(s):

K. Kovacs ◽

E. Horvath

Keyword(s):

Pituitary Adenomas ◽

Secretory Activity ◽

Microscopic Investigation ◽

Uranyl Acetate ◽

Electron Microscopic Investigation ◽

Electron Microscopic ◽

Human Pituitary ◽

Cytoplasmic Staining ◽

Human Pituitary Gland ◽

Microscopic Features

Chromophobe pituitary adenomas arise from adenohypophysial cells and fail to exhibit cytoplasmic staining with conventional acid or basic dyes by light microscopy. The aim of the present work was to study the electron microscopic features of these tumors, to separate them into distinct entities and to correlate their fine structural appearances with secretory activity.Among 48 surgically removed various pituitary adenomas 30 tumors were found which, based on the tinctorial characteristics of the cytoplasm, corresponded to chromophobe adenomas. For electron microscopic investigation pieces of these tumors were fixed in 2.5 per cent glutaraldehyde in Sorensen's buffer, post fixed in 1 per cent osmium tetroxide in Millonig's buffer, dehydrated in graded ethanol and embedded in Epon 812. Ultrathin sections were stained with uranyl acetate and lead citrate.By electron microscopy it was possible to separate chromophobe adenomas into 3 distinct entities: 1) adenomas consisting of sparsely granulated growth hormone cells (7 cases).

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Abstract #826 Sox 2 Expression in Human Pituitary Adenomas

Endocrine Practice ◽

10.1016/s1530-891x(20)47313-6 ◽

2018 ◽

Vol 24 ◽

pp. 186

Author(s):

Cristina Capatina ◽

Anca Campeanu ◽

Marius Raica ◽

Mihail Coculescu ◽

Catalina Poiana

Keyword(s):

Pituitary Adenomas ◽

Human Pituitary ◽

Human Pituitary Adenomas

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Assessment of endocrine disorders of the hypothalamicpituitary axis by nuclear medicine techniques

Nuklearmedizin ◽

10.1055/s-0038-1625645 ◽

2002 ◽

Vol 41 (02) ◽

pp. 80-90 ◽

Cited By ~ 2

Author(s):

F. Jockenhövel ◽

P. Theissen ◽

M. Dietlein ◽

W. Krone ◽

H. Schicha ◽

...

Keyword(s):

Nuclear Medicine ◽

Pituitary Adenomas ◽

Dopamine D2 Receptor ◽

Somatostatin Receptor ◽

D2 Receptor ◽

Ectopic Acth Syndrome ◽

Endocrine Disorders ◽

Ectopic Acth ◽

Number Of Patients ◽

Hypothalamic Pituitary Axis

SummaryThe following article reviews nuclear medicine techniques which can be used for assessment of endocrine disorders of the hypothalamic-pituitary axis. For planar and SPECT imaging somatostatin-receptor- and dopamine- D2-receptor-scintigraphy are the most widely distributed techniques. These nuclear medicine techniques may be indicated in selected cases to answer differential diagnostic problems. They can be helpful to search for presence and localization of receptor positive tissue. Furthermore they can detect metastasis in the rare cases of a pituitary carcinoma. Scintigraphy with Gallium-67 is suitable for further diagnostic evaluation in suspected hypophysitis. Other SPECT radiopharmaca do not have relevant clinical significance. F-18-FDG as PET radiopharmacon is not ideal because obvious pituitary adenomas could not be visualized. Other PET radiopharmaca including C-11-methionine, C-11-tyrosine, F-18-fluoroethylspiperone, C-11-methylspiperone, and C-11-raclopride are available in specialized centers only. Overall indications for nuclear medicine in studies for the assessment of endocrine disorders of the hypothalamic-pituitary-axis are rare. Original studies often report only about a small number of patients. According to the authors’ opinion the relevance of nuclear medicine in studies of clinically important endocrinologic fields, e. g. localization of small ACTH-producing pituitary adenomas, tumor localization in ectopic ACTH syndrome, localization of recurrent pituitary tissue, assessment of small incidentalomas, can not be definitely given yet.

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