Abstract
Papillary thyroid cancer (PTC) is the most common tumor subtype of thyroid cancer. However, not all PTCs are responsive to current surgical and radioiodine treatment. The well-established clinical prognostic factors include tumor size, lymph node/distal metastasis, and extrathyroidal invasion. The RET/PTC-RAS-BRAF linear molecular signaling cascade is known to mediate PTC pathogenesis. However, whether presence of BRAF mutation, the most common genetic alteration in PTC, can affect PTC behavior and prognosis is controversial. MicroRNAs (miRNAs) have been labeled as promising molecular prognostic markers in several tumor types. Our recent studies demonstrated that microRNA-146b (miR-146b) deregulation is associated with PTC aggressiveness and prognosis. Here we summarize the current knowledge related to the functional roles, regulated target genes, and clinical applications of miR-146b in PTC and discuss how these studies provide insights into the key role of miR-146b as an oncogenic regulator promoting cellular transformation as well as a prognosis marker for tumor recurrence in PTC. In conjunction with the current perspectives on miRNAs in a wide variety of human cancers, this review will hopefully translate these updated findings on miR-146b into more comprehensive diagnostic or prognostic information regarding treatment in PTC patients before surgical intervention and follow up strategies.
Highlights
The prevalence of thyroid cancer has increased over time from the worldwide reports; the majority of thyroid cancers are papillary thyroid carcinoma (PTC), which is clinical-pathogenically heterogeneous in tumor behavior or prognosis [1,2]
Sancisi et al [10] studied BRAFV600E mutation in metastatic PTC and found that the BRAFV600E mutation was present in 29.8% of the distantly metastatic PTC, whereas it was detected in about 44.0% of the control tumors, suggesting that the BRAF mutation was of no significance for active disease progression
The accumulating reports raise an appealing concept that sequence-specific inhibition of miRs in stem/progenitor cell populations can deliver a potential therapeutic strategy for modulation of stem/progenitor cells whose miRs are deregulated in cancer
Summary
The prevalence of thyroid cancer has increased over time from the worldwide reports; the majority of thyroid cancers are papillary thyroid carcinoma (PTC), which is clinical-pathogenically heterogeneous in tumor behavior or prognosis [1,2]. A microRNA array study [19] demonstrated that deregulation of microRNA-146b (miR-146b) was significantly associated with aggressive tumor behavior in BRAF-positive clinical PTC specimens. In order to delineate the role of miR-146b in EMT by augmenting PTC cancer cell migration/invasion, we identified a regulatory mechanism linking miR-146b and its target gene IRAK1 in PTC cell lines [37]. The function of the miR-146b-IRAK1 axis may be potentially associated with EMT by regulation of E-cadherin in PTC cancer cell lines. In agreement with our findings, Lima et al [38] reported that miR-146b positively regulates migration and invasion activity both in normal or cancer thyroid lines through the action of stimulating actin cytoskeleton functions. Wang et al [40] reported that p21 is regulated by miR-146b and leads to tumor proliferation and migration in anaplastic thyroid cancer (ATC) cells. Papillary thyroid cancer; ATC, anaplastic thyroid cancer; FTC, follicular thyroid carcinoma; EMT, epithelialmesenchymal transition
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
