scholarly journals Deregulation of microRNA expression in follicular cell-derived human thyroid carcinomas

2010 ◽  
Vol 17 (1) ◽  
pp. F91-F104 ◽  
Author(s):  
Pierlorenzo Pallante ◽  
Rosa Visone ◽  
Carlo Maria Croce ◽  
Alfredo Fusco

Carcinoma of the thyroid gland is an uncommon cancer, but one of the most frequent malignancies of the endocrine system. Most thyroid cancers are derived from the follicular cells. Follicular carcinoma is considered more malignant than papillary thyroid carcinoma (PTC), and anaplastic thyroid cancer (ATC) is one of the most lethal human cancers. Even though several genetic lesions have been already described in human thyroid cancer, particularly in the papillary histotype, the mechanisms underlying the development of these neoplasias are still far from being completely elucidated. Some years ago, several studies were undertaken to analyze the expression of microRNAs (miRNAs or miRs) in thyroid carcinoma to evaluate a possible role of their deregulation in the process of carcinogenesis. These studies showed an aberrant microRNA expression profile that distinguishes unequivocally among PTC, ATC, and normal thyroid tissue. Here, other than summarizing the current findings on microRNA expression in human thyroid carcinomas, we discuss the mechanisms by which microRNA deregulation may play a role in thyroid carcinogenesis, and the possible use of microRNA knowledge in the diagnosis and therapy of thyroid neoplasms.

1998 ◽  
Vol 83 (11) ◽  
pp. 4102-4106 ◽  
Author(s):  
Bernard Caillou ◽  
Frédéric Troalen ◽  
Eric Baudin ◽  
Monique Talbot ◽  
Sébastiano Filetti ◽  
...  

Antipeptide antibodies raised against the carboxyl-terminal region of the human sodium/iodide (Na+/I−) symporter (hNIS) were used to investigate by immunohistochemistry the presence and distribution of the hNIS protein in normal thyroid tissues, in some pathological nonneoplastic thyroid tissues, and in different histotypes of thyroid neoplasms. In normal thyroid tissue, staining of hNIS protein was heterogeneous and limited to a minority of follicular cells that were in close contact with capillary vessels. In positive cells, immunostaining was limited to the basolateral membrane. In contrast, in Graves’ disease the majority of follicular cells expressed the hNIS protein. In autoimmune thyroiditis, the number of hNIS-positive cells, was similar to that found in normal tissue. These positive cells were found essentially close to lymphocytic infiltrates. This observation supports the concept of hNIS as an autoantigen. In diffuse nodular hyperplasia, hNIS staining was heterogeneous, but the number of hNIS-positive cells exceeded that found in normal tissue. In well differentiated follicular or papillary carcinoma, the number of hNIS-positive cells was significantly lower than in normal tissue. In poorly differentiated follicular carcinoma, the number of hNIS-positive cells was less than that found in well differentiated carcinoma, or there were no positive cells. Interestingly, in all of these thyroid tissues, the number of follicular cells exhibiting TSH receptor (TSHR) immunoreactivity was greater than the number of hNIS-positive cells. As hNIS expression appears to be related to TSHR stimulation, the decreased number of TSHR-positive cells in cancers may contribute to the reduced capacity of neoplastic cells to concentrate iodide. In one patient with a follicular cancer with an absence of hNIS immunostaining, the total body 131I scan showed no uptake in metastatic tissue. In three cancers with positive hNIS cells, the 131I scan showed uptake in lymph node metastases. This suggests that immunodetection of hNIS could predict radioiodine uptake in thyroid cancers.


1992 ◽  
Vol 132 (3) ◽  
pp. 461-468 ◽  
Author(s):  
C. P. Verschueren ◽  
G. R. Rutteman ◽  
J. H. Vos ◽  
J. E. Van Dijk ◽  
T. W. A. de Bruin

ABSTRACT Thyrotrophin (TSH) is the conditional growth factor of thyroid epithelial cells. Abnormalities in TSH-receptor binding such as a low receptor number or low binding affinity may be a marker of thyroid carcinoma or metastases, or may exhibit a relationship with the functional variability of such tissues. The dog was used as a model to characterize TSH-receptor binding in normal thyroid tissues, naturally occurring thyroid neoplasms and distant metastases. In normal dog thyroid tissues, specific 125I-labelled TSH binding ranged from 2·7 to 15·5%, and low cross-reactivity with bovine LH (0·023%) was observed. One class of TSH-binding sites was found in eight normal thyroid tissues and 22 thyroid carcinomas; two normal thyroid tissues and one tumour exhibited two classes of binding sites. The concentration of binding sites was lower in the five carcinomas with reduced pertechnetate uptake (0·09 pmol/mg protein) than in the five thyroid neoplasms with increased uptake (0·19 pmol/mg) (P= 0·055). Compared with the original carcinoma tissues, TSH binding revealed a reduced binding affinity in eight out of eleven metastases. Two metastases showed a complete absence of TSH binding, suggesting that they were not dependent on TSH for growth. We conclude that one class of TSH-binding site is predominant in normal dog thyroid tissues and dog thyroid carcinomas. TSH could therefore contribute, at least in theory, to further growth of primary dog thyroid carcinomas. Secondly, assays measuring TSH binding may not be able to discriminate between malignant and benign dog thyroid tumours. TSH receptor number or affinity may be related to the functional variability of thyroid neoplasms. The absence of TSH binding in some metastases demonstrated that this characteristic can be acquired during the natural history of a differentiated thyroid carcinoma. Journal of Endocrinology (1992) 132, 461–468


1997 ◽  
Vol 82 (12) ◽  
pp. 4094-4100
Author(s):  
Lisa Fiore ◽  
Luca E. Pollina ◽  
Gabriella Fontanini ◽  
Rosario Casalone ◽  
Maria T. Berlingieri ◽  
...  

A human anaplastic thyroid cancer cell line FB-1, derived from a 68-yr-old woman who underwent surgery for anaplastic thyroid cancer, has been established. The spindlelike cells have been proliferating stably for more than 2 yr. Karyotype analysis shows many abnormalities and many marker chromosomes have been observed. Heterotransplant of FB-1 cells into severe combined immunodeficient mice has resulted in rapidly growing tumors classified as anaplastic carcinomas, although 50% have shown areas with a trabecular pattern. FB-1 cells failed to express messenger RNA for thyroglobulin; TSH-receptor; thyroperoxidase, and placental angiogenic growth factor. Conversely, PAX8 and thyroid transcription factor 1, whose expression is thyroid specific, was kept in an FB-1 cell line at a level comparable with that observed in normal thyroid tissue. In addition, the present cell line expressed high levels of messenger RNA for high-mobility group proteins (Y) and -C. The in vitro study revealed that FB-1 cells are able to produce high levels of interleukin (IL)-8 and medium amount of IL-6, whereas no release of IL-1-α, IL-1-β, and IL-4 was observed. No modulation of cell proliferation and DNA synthesis in FB-1 cells has been observed after the addition of exogenous IL-6.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yitian Li

Abstract Background Anaplastic thyroid carcinoma is a highly lethal subtype of thyroid cancer without effective therapies. Drug resistance in anaplastic thyroid carcinoma poses a significant problem. Although artemisinin exerts antitumor effects, but its efficacy in anaplastic thyroid carcinoma is unknown. Methods We used RNA sequencing to identify differentially expressed genes. Next, we determined the cause of ART resistance by testing the expression and activity of β-catenin, and enhanced ART activity with a WNT signaling inhibitor. Results Artemisinin suppressed the growth of BHT-101 but not human thyroid anaplastic carcinoma (CAL-62) cells. The mechanism of artemisinin resistance in CAL-62 was associated with the aberrant activation of WNT signaling. Pyrvinium pamoate, an inhibitor of WNT signaling, was used to overcome ART resistance in CAL-62 cells. The combination of artemisinin and pyrvinium pamoate suppressed the growth of CAL-62 cells and induced the apoptosis. Conclusions Our study is the first to prove the efficacy of ART as monotherapy or in combination with PP in the management of anaplastic thyroid cancer, and that the inhibition of WNT signaling may overcome ART resistance.


2005 ◽  
Vol 90 (2) ◽  
pp. 928-935 ◽  
Author(s):  
Rosanna Sorrentino ◽  
Silvana Libertini ◽  
Pier Lorenzo Pallante ◽  
Giancarlo Troncone ◽  
Lucio Palombini ◽  
...  

Alterations in chromosome number (aneuploidy) are common in human neoplasias. Loss of mitotic regulation is believed to induce aneuploidy in cancer cells and act as a driving force during the malignant progression. The serine/theronine protein kinases of aurora family genes play a critical role in the regulation of key cell cycle processes. Aurora B mediates chromosome segregation by ensuring orientation of sister chromatids and overexpression of Aurora B in diploid human cells NHDF (normal human diploid fibroblast) induces multinuclearity. We analyzed Aurora B expression in human thyroid carcinomas. Cell lines originating from different histotypes showed an increase in Aurora B expression. Immunohistochemical analysis of archive samples showed a high expression of Aurora B in anaplastic thyroid carcinomas; conversely, Aurora B expression was not detectable in normal thyroid tissue. Real-time PCR analysis confirmed a strong expression of Aurora B in anaplastic thyroid carcinomas. The block of Aurora B expression induced by RNA interference or by using an inhibitor of Aurora kinase activity significantly reduced the growth of thyroid anaplastic carcinoma cells.


e-CliniC ◽  
2016 ◽  
Vol 4 (2) ◽  
Author(s):  
Yolanda Parura ◽  
Victor Pontoh ◽  
Marselus Werung

Abstract: Thyroid cancer is a common malignant disease found in endocrine system and is increasing in incidence every year, in Indonesia found around 9 from 10 malignancy. Based on histopathological types, thyroid carcinomas are divided into papillary carcinoma, follicular carcinoma, medullary carcinoma, and anaplastic carcinomas. The most common are papillary carcinoma and then follicular carcinoma. Factors that can influence the histopathological type of thyroid carcinomas is geographical factor, which most commonly found in mountainous areas. Thyroid cancer is rare in men, most often in women with a ratio of 1: 3.Conclusion: Female gender, mountainous terrain and adulthood to older people who suffered most thyroid cancer. Keywords: thyroid cancer Abstrak: Kanker tiroid penyakit keganasan tersering ditemukan pada sistim endokrin dan insidennya meningkat setiap tahun, di Indonesia menempati urutan 9 dari 10 keganasan yang sering ditemukan. Berdasarkan gambaran histopatologinya, karsinoma tiroid dibagi menjadi tipe papiler, folikuler, meduler, dan anaplastik. Kasus terbanyak adalah karsinoma tiroid papiler dan terbanyak kedua adalah karsinoma tiroid folikular. Salah satu faktor yang mempengaruhi gambaran histopatologi karsinoma tiroid adalah keadaan geografis, dimana paling banyak ditemukan pada daerah pegunungan. Kanker tiroid jarang terjadi pada laki-laki, paling sering pada perempuan dengan perbandingan 1:3. Simpulan: Jenis kelamin perempuan, daerah pegunungan dan usia dewasa sampai lanjut usia yang paling banyak menderita kanker tiroid. Kata kunci: kanker tiroid


2020 ◽  
Vol 11 (1) ◽  
pp. 54-58
Author(s):  
AKM Farhad Hossain ◽  
Md Mahmudur Rahman Siddiqui ◽  
Sayada Fatema Khatun

Background: Thyroid cancer is the most common malignant disease in endocrine system. It is an emerging public health issue associated with burden on the family, community and the nation. The aim of this study is to determine the socio-demographic and clinical characteristics of patient with thyroid cancer attending in tertiary hospital. Methods: This cross sectional study was conducted among 246 thyroid cancer patients in two tertiary hospitals of Dhaka city from 01 July 2018 to 30 June 2019. The subjects were selected purposively following specific selection criteria and maintaining ethical issues. Data were collected by face to face interview using a semi-structured questionnaire and checklist. Data were analyzed by the statistical package for the social science (SPSS) version 23. Results: This study revealed that majority (74.4%) of respondents was female, married (72%), housewife (61.4%), rural respondent (41.1%) and had primary education (69%). Mean (± SD) age of the respondent was 37.85(±12.20) years (Range 14-70 years) and mean (± SD) monthly family income was Tk. 17681(±10602). Out of 246 cases, 204 (82.9%) was papillary and 42 (17.1%) was follicular carcinoma. Various clinical presentations included visible neck swelling in 225 (91.5%), swollen lymph node in 103 (41.9%), pain 90 (36.6%), Difficulties in swallowing 87 (35.4%), Hoarseness of voice in 141 (57.3%), cough along with swelling 47(19.1%), Difficulties in breathing due to swelling in 13(5.3%) of the patients. Conclusion: Incidence of thyroid cancer has increased worldwide specially in female patients in 3rd and 4th decades of life. As thyroid cancer is a growing public health problem in Bangladesh, proper screening and early diagnostic facilities at all level should be available to measure its actual burden in the country. Anwer Khan Modern Medical College Journal Vol. 11, No. 1: Jan 2020, P 54-58


2004 ◽  
Vol 7 (5) ◽  
pp. 487-492 ◽  
Author(s):  
Van H. Savell ◽  
Stephen M. Hughes ◽  
Charles Bower ◽  
David M. Parham

Lymphocytic thyroiditis has been associated with an increase in the incidence of thyroid papillary carcinoma in some reports, mostly series of both adults and children. Relatively little is written about thyroiditis and follicular carcinomas. We have seen several cases of pediatric follicular thyroid carcinomas, that had an associated lymphocytic infiltrate, which led us to examine all primary malignant thyroid neoplasms in our surgical files from 1984 through 2000 to examine this relationship. We also investigated the nature of the lymphocytic infiltrate with routine immunohistochemistry. Ten patients (five male, five female, ages 4.5–21 years of age) had a thyroid carcinoma resection, six (three males and three females) with papillary carcinoma and four patients (two males and two females) with low-grade follicular carcinoma. Seven samples (one male had two cases with tumor) from patients who had a papillary carcinoma resection with tissue blocks available were identified (one patient had slides but no blocks), as were all four patients with a follicular carcinoma. The thyroid of all patients with a follicular carcinoma contained a lymphocytic infiltrate; only four of the seven papillary carcinoma samples had an associated lymphoid infiltrate. In all cases with a lymphoid infiltrate, the infiltrate was present in both lobes (both adjacent and separate from the tumor). B lymphocytes were present in the lymphoid infiltrate of three of four patients with follicular carcinomas and in 1 of 3 cases of papillary carcinomas. T cells were dispersed throughout all the tumors with lymphoid infiltrates. We conclude that pediatric follicular carcinomas have an associated lymphocytic infiltrate in the tumor and/or adjacent thyroid, more commonly than papillary carcinomas.


Author(s):  
Dumitru A Iacobas

Publically available (own) transcriptomic data were re-analyzed to quantify the alteration of functional pathways in the thyroid cancer, establish the gene hierarchy, identify potential gene targets and predict the effects of their manipulation. The expression data were generated from one case of papillary thyroid carcinoma (PTC) and from genetically manipulated BCPAP (papillary) and 8505C (anaplastic) human thyroid cancer cell lines. The study used the genomic fabric perspective that considers the transcriptome as a multi-dimensional mathematical object based on the three independent characteristics that can be derived for each gene from the expression data. We found remarkable remodeling of the thyroid hormone synthesis, cell cycle, oxidative phosphorylation and apoptosis pathways. Serine peptidase inhibitor, Kunitz type, 2 (SPINT2) was identified as the Gene Master Regulator of the investigated PTC. The substantial increase of the expression synergism of SPINT2 with apoptosis genes in the cancer nodule with respect to the surrounding normal tissue (NOR) suggests that its experimental overexpression may force the PTC cells into apoptosis with negligible effect on the NOR cells. The predictive value of the expression coordination for the expression regulation was validated with data from 8505C and BCPAP cells before and after lentiviral transfection with DDX19B.


2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Bo Gao ◽  
Lingji Guo ◽  
Donglin Luo ◽  
Yan Jiang ◽  
Jianjie Zhao ◽  
...  

Thyroid cancer is the most common endocrine cancer, and has a high incidence of lymphatic metastasis. Vascular endothelial growth factor C (VEGFC) is essential for development of lymphatic vessels and lymphatic metastases during carcinogenesis. Steroid receptor coactivator-1 (SRC-1) interacts with nuclear receptors and transcription factors to promote tumor proliferation and metastasis. However, the correlation between SRC-1 and VEGFC levels in the lymphatic metastases of thyroid cancer remains unclear. We analyzed 20-paired specimens of thyroid cancer tissue and normal thyroid tissue and found increased levels of SRC-1 and VEGFC proteins in 13/20 and 15/20 thyroid cancer specimens, respectively, when compared with those levels in specimens of normal thyroid tissue. A high level of SRC-1 expression was positively correlated with VEGFC and lymphatic endothelial cell marker LYVE-1 expression. Papillary thyroid carcinoma cell line TPC-1 displayed high levels of SRC-1 and VEGFC expression and was selected for stable knockdown of SRC-1 in vitro. Inhibition of SRC-1 significantly reduced the VEGFC levels in TPC-1 cells. We found that SRC-1 binds to transcription factor NF-kB (p50/p65), and that this coactivation complex directly promoted VEGFC transcription, which could be abrogated by SRC-1 knockdown. Up-regulated NF-kB signaling was also confirmed in thyroid cancer tissues. In vivo studies showed that SRC-1 knockdown restricted tumor growth, reduced the numbers of LYVE-1-positive lymphatic vessels, and decreased the levels of VEGFC in tumor tissues. These results suggest a tumorigenic role for SRC-1 in thyroid cancer via its ability to regulate VEGFC expression.


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