Noncoding RNAs in Thyroid-Follicular-Cell-Derived Carcinomas

Abstract

Among the thyroid neoplasias originating from follicular cells, we can include well-differentiated carcinomas, papillary (PTC) and follicular (FTC) thyroid carcinomas, and the undifferentiated anaplastic (ATC) carcinomas. Several mutations in oncogenes and tumor suppressor genes have already been observed in these malignancies; however, we are still far from the comprehension of their full regulation-altered landscape. Even if only 2% of the human genome has the ability to code for proteins, most of the noncoding genome is transcribed, constituting the heterogeneous class of noncoding RNAs (ncRNAs), whose alterations are associated with the development of several human diseases, including cancer. Hence, many scientific efforts are currently focused on the elucidation of their biological role. In this review, we analyze the scientific literature regarding the involvement of microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and pseudogenes in FTC, PTC, and ATC. Recent findings emphasized the role of lncRNAs in all steps of cancer progression. In particular, lncRNAs may control progression steps by regulating the expression of genes and miRNAs involved in cell proliferation, apoptosis, epithelial–mesenchymal transition, and metastatization. In conclusion, the determination of the diagnosis, prognosis, and treatment of cancer based on the evaluation of the ncRNA network could allow the implementation of a more personalized approach to fighting thyroid tumors.

MicroRNA expression profiling of RAS-mutant thyroid tumors with follicular architecture: microRNA signatures to discriminate benign from malignant lesions

“…Comparing the FAs versus all the malignant lesions, 22 miRNAs showed significant deregulation. Among these, the most widely described as up-regulated in thyroid cancer are miR-146b-5b , miR-221 , miR-181 , and miR99b [ 10 , 11 , 13 ]; on the other hand, the most well-known downregulated miRNAs are miR144 , miR-451a , miR-497 , miR-195 , miR-143 , and miR-152 [ 13 ]. The analysis of enriched pathways showed that the 22 miRNAs deregulated in malignant RAS -positive thyroid tumors play a key role in several cancer-related pathways.…”

“…Considering miR-144-3p , its overexpression inhibits proliferation, migration, and invasion of thyroid cancer cells in vitro [ 37 ]. Although the majority of reports found that miR-144-3p is downregulated [ 10 , 13 , 23 , 34 ], there are few studies reporting that miR-144-3p is overexpressed in thyroid cancer [ 38 , 39 ]; in one study, the overexpression of miR-144-3p was inversely correlated with the transcript quantity of the tumor suppressor gene PTEN [ 38 ]. In our study, miR-144-3p was significantly down-regulated in all the RAS -mutant malignant tumors compared to RAS -mutant FAs, therefore our report supports the evidence that miR-144-3p acts as a tumor suppressor miRNA.…”

“…MiRNAs can behave both as oncomiR and tumor suppressors, according to their mRNA targets [9]. Over the past 20 years, several miRNAs have been proposed as effective markers for the differential diagnosis of indeterminate thyroid nodules and for the prognostic stratification of tumors; also, miRNAs differentially expressed in a histotype-specific manner have been reported [10]. Across the considerable amount of data on miRNA expression analysis in thyroid tumors, there are few miRNAs widely and consistently reported as deregulated in thyroid cancer, including the overexpression of miR-146, miR-221, miR-222, and miR-181 [11][12][13].…”

Potential Role of Selected miRNAs in the Pathogenesis of Autoimmune Thyroid Diseases in Children and Adolescents

“…RNA encodes most of the non-coding genome. Mutations in RNA can cause many human diseases, including autoimmunity, or cancer [6].…”

Problems of follicular thyroid carcinoma diagnostics

“…Становится очевидным, что для повышения точности молекулярно-генетических тестов необходим поиск новых геномных изменений, высокоспецифичных для ФРЩЖ. В настоящее время во многом мутации и транслокации довольно хорошо изучены, при этом в ряде случаев их наличие или отсутствие не может считаться надежным диагностическим критерием дифференциальной диагностики, в связи с чем дальнейший поиск генетических маркеров для ФРЩЖ может быть направлен, например, на эпигенетические маркеры, такие как микроРНК [14].…”