Differential MicroRNA-Signatures in Thyroid Cancer Subtypes

Abstract

Thyroid cancer is one of the most common endocrine cancers, with an increasing trend in the last few decades. Although papillary thyroid cancer is the most frequent subtype compared with follicular or anaplastic thyroid cancer, it can dedifferentiate to a more aggressive phenotype, and the recurrence rate is high. The cells of follicular adenomas and follicular carcinomas appear identical in cytology, making the preoperative diagnosis difficult. On the other hand, anaplastic thyroid cancer poses a significant clinical challenge due to its aggressive nature with no effective therapeutic options. In the past several years, the roles of genetic alterations of thyroid tumors have been documented, with a remarkable correlation between genotype and phenotype, indicating that distinct molecular changes are associated with a multistep tumorigenic process. Besides mRNA expression profiles, small noncoding microRNA (miRNA) expression also showed critical functions for cell differentiation, proliferation, angiogenesis, and resistance to apoptosis and finally activating invasion and metastasis in cancer. Several high-throughput sequencing studies demonstrate that miRNA expression signatures contribute clinically relevant information including types of thyroid cancer, tumor grade, and prognosis. This review summarizes recent findings on miRNA signatures in thyroid cancer subtypes.

Molecular Genetics of Follicular-Derived Thyroid Cancer

“…It has been demonstrated that up-regulated miRNAs target suppressor genes, such as PTEN , belonging to the MAPK and the PI3K/AKT pathways [ 54 ]. On the contrary, suppressor miRNAs have been frequently reported as down-regulated in thyroid cancer (for instance miR-375, miR-7 and miR204) [ 55 , 56 ]. Moreover, since miRNAs are differentially expressed in thyroid tumors versus benign lesions and in different histotypes of thyroid cancer, the development of miRNA-based molecular test is an appealing strategy for the diagnostic and prognostic definition of thyroid tumors [ 57 ].…”

miR‑122‑5p suppresses the oncogenesis of PTC by inhibiting DUSP4 expression

“…The association analyses between miR-122-5p expression and clinicopathological characteristics revealed that the reduced expression of miR-122-5p indicated poor overall survival. Previous studies have revealed several miRNAs that can predict the prognosis of PTC, including miR-599 and miR-215 (3,4,24,25). Thus, the aforementioned data suggested that miR-122-5p may be a novel promising prognostic biomarker for PTC.…”

Molecular Markers Guiding Thyroid Cancer Management

“…MiRNAs have been classified into a group of oncogenic and tumour suppressor miRNAs, which are based on their expression profile and their effect on cancer related signalling pathways [28,131,132]. The upregulation of oncogenic MiRNAs inhibits apoptosis and induce cell proliferation and growth, invasion and metastases by modulating target genes of several signalling pathways such as the PI3K/AKT/mTOR-, adipocytokine-, Hippo-, Wnt/β-catenin-signalling pathways [28]. In contrast, downregulation of tumour suppressor miRNAs results in loss of inhibition of cell proliferation and migration, and EMT in the MAPK, PI3K/AKT, NFκB or GSK-3β/β-catenin pathways [27,[131][132][133][134].…”

“…In contrast, downregulation of tumour suppressor miRNAs results in loss of inhibition of cell proliferation and migration, and EMT in the MAPK, PI3K/AKT, NFκB or GSK-3β/β-catenin pathways [ 27 , 131 , 132 , 133 , 134 ]. Although miRNA have extensively been studied in PTC, distinct miRNA patterns were identified in different TC subtypes targeting different target genes [ 28 ]. Some examples of target genes in PTC are Zinc Ring Finger 3 (ZNRF3)- , cytokine receptor KIT- or the CXCL12 gene [ 27 , 134 , 135 ].…”

“…An example of evolving biomarkers for diagnosis and prognosis in TC are MicroRNAs (miRNA). By regulating target genes of various signalling pathways including gene expression of known oncogenes and tumour suppressor genes, they play a crucial role for cell differentiation, migration, invasion and even epithelial-to-mesenchymal transition (EMT) [26][27][28]. Furthermore, different and distinct miRNA profiles were identified in different TC subtypes [28][29][30][31][32][33].…”