scholarly journals Epigenetic Silencing of SOX15 Is Controlled by miRNAs rather than Methylation in Papillary Thyroid Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Ahmet Ozaydin ◽  
Aysegul Soysal ◽  
Betul Seyhan ◽  
Soykan Arikan ◽  
Nejat Dalay ◽  
...  

Object. Thyroid cancer (TC) is a rare type of cancer which occurs as a result of environmental and genetic factors. Although different types of genetic and epigenetic changes are associated with TC, the molecular mechanism still remains unclear. SRY-box transcription factor 15 (SOX15) is an important transcription factor, and its expression is altered in many cancer types by epigenetic modifications. Recently, miR-147b overexpression has been associated with SOX15 silencing in TC. Methods. In this study, qRT-PCR was used to investigate the expression levels of the SOX15 gene and of miR-182, miR-183, miR-375, and miR-96 in thyroid tumors and adjacent noncancerous tissues. We also investigated the methylation status of the SOX15 promoter by methylation-specific PCR in tumors and adjacent noncancerous tissues. Results. We observed a statistically significant downregulation of SOX15 expression in tumors compared to noncancerous tissue samples. The methylation levels of tumors and matched noncancerous tissues were similar, but miR-182, miR-183, and miR-375 expression levels were elevated in tumor tissues compared to noncancerous tissue samples. Conclusions. Our results indicate that SOX15 gene expression is associated with the pathogenesis of papillary thyroid carcinoma (PTC), and the epigenetic control of the SOX15 gene is regulated by miRNAs rather than by promoter methylation.

2021 ◽  
Author(s):  
Yang Zhao ◽  
Cangang Zhang ◽  
Yanan Zhu ◽  
Xi Ding ◽  
Yikun Zhou ◽  
...  

The immunosuppressive microenvironment is associated with poor prognosis in papillary thyroid cancer (PTC); however, the molecular mechanisms involved are unknown. Among triggering receptor expressed on myeloid cell (TREM) family, we found that TREM1 expression in PTC was significantly higher than that in normal tissues. TREM1 overexpression was associated with BRAFV600E profiles and advanced tumor stages. Furthermore, TREM1 mRNA expression was negatively correlated with promoter methylation status. Specifically, hypomethylation of CpG site cg06196379 in the TREM1 promoter was related with poor patient disease free survival (DFS) and a high PTC recurrence rate. Mechanistically, TREM1 was mainly expressed in malignant epithelial cells but not macrophages in PTC by single-cell analysis. PTC tissues with high TREM1 levels had enhanced infiltration of regulatory T cells (Tregs) and decreased infiltration of CD8+ T cells. Our study confirms that hypomethylation-mediated overexpression of TREM1 in PTC cells promotes an immunosuppressive microenvironment by enhancing Treg infiltration. We recommend the future use of therapeutic strategy targeting TREM1 for the treatment of PTC.


2010 ◽  
Vol 23 (8) ◽  
pp. 1052-1060 ◽  
Author(s):  
Monica Zerilli ◽  
Giovanni Zito ◽  
Anna Martorana ◽  
Maria Pitrone ◽  
Daniela Cabibi ◽  
...  

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Birute Zilaitiene ◽  
Aiste Kondrotiene ◽  
Daina Pamedytyte ◽  
Vaida Simanaviciene ◽  
Dalia Dauksiene ◽  
...  

Abstract Introduction.: There is no effective and reliable biomarker to distinguish benign thyroid nodules (BTN) from papillary thyroid carcinomas (PTC). In this study we analyzed a set of four miRNA molecules in plasma of patients with papillary thyroid cancer, benign nodules and healthy controls to identify miRNA molecules that may be markers of PTC.Aim.: We aimed to investigate the dysregulation of plasma miRNAs in PTC and evaluate the diagnostic value for differentiation of PTC from BTN. Methods.: The expression levels of 4 miRNAs (miR-221, miR-222, miR-146b, miR-21) were measured in 48 PTC patients before thyroidectomy and again after thyroidectomy in a subgroup of 36 patients. Preoperative and postoperative plasma miRNA expression levels were compared with baseline levels established in plasma from the heathy controls group (N=57) and patients with BTN (N=22). MicroRNA-222 and miR-146b, miR-221, miR-21 were included in a panel because they all reportedly were overexpressed in PTC compared to benign nodules or normal thyroid tissue.Results.: Compared with baseline levels in the healthy controls group, miR-221, miR-222, miR-146b, miR-21 levels were significantly higher in the preoperative PTC group (P <0.0001, P=0.002, P=0.028, P =0.021, respectively). A significant reduction in miR-21 expression was observed in postoperative PTC patients. MiR-21 decreased by 5.98-fold (P=0.046) in post- operative samples compared with preoperative samples in the PTC patients.In comparison MiRNRs expression levels in BTN group with healthy controls, miR-221, miR-21 expression levels were significantly higher in the BTN group (P=0.003, P=0.048, respectively). No significant difference was observed between the preoperative PTC group and the preoperative BTN group with regard to the expression of these four miRNA’s. Conclusions: The expression levels of miR-222, miR-146b in plasma were significantly higher in patients who had PTC than in healthy volunteers, whereas levels of miR-221, miR-21 in plasma were significantly higher in patients who had either PTC or BTN before thyroidectomy than in healthy volunteers. Furthermore, miR-21 showed a significant reduction of expression levels after thyroidectomy in PTC patients. However, value of these four miRNAs is still limited in differential diagnosis of PTC and benign nodules.


Thyroid ◽  
2005 ◽  
Vol 15 (10) ◽  
pp. 1137-1146 ◽  
Author(s):  
Michal Ambroziak ◽  
Janusz Pachucki ◽  
Elżbieta Stachlewska-Nasfeter ◽  
Janusz Nauman ◽  
Alicja Nauman

Oral Oncology ◽  
2015 ◽  
Vol 51 (1) ◽  
pp. 77-83 ◽  
Author(s):  
Yoon Se Lee ◽  
Yun Sung Lim ◽  
Jin-Choon Lee ◽  
Soo-Geun Wang ◽  
Hee-Young Park ◽  
...  

Neoplasia ◽  
2018 ◽  
Vol 20 (11) ◽  
pp. 1121-1134 ◽  
Author(s):  
Oorvashi Roy Puli ◽  
Brian P Danysh ◽  
Elena McBeath ◽  
Deepankar K Sinha ◽  
Nguyet M Hoang ◽  
...  

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