Role of microRNAs in endocrine cancer metastasis

Abstract

The deregulation of transcription and processing of microRNAs (miRNAs), as well as their function, has been involved in the pathogenesis of several human diseases, including cancer. Despite advances in therapeutic approaches, cancer still represents one of the major health problems worldwide. Cancer metastasis is an aggravating factor in tumor progression, related to increased treatment complexity and a worse prognosis. After more than one decade of extensive studies of miRNAs, the fundamental role of these molecules in cancer progression and metastasis is beginning to be elucidated. Recent evidences have demonstrated a significant role of miRNAs on the metastatic cascade, acting either as pro-metastatic or anti-metastatic. They are involved in distinct steps of metastasis including epithelial-to-mesenchymal transition, migration/invasion, anoikis survival, and distant organ colonization. Studies on the roles of miRNAs in cancer have focused mainly on two fronts: the establishment of a miRNA signature for different tumors, which may aid in early diagnosis using these miRNAs as markers, and functional studies of specific miRNAs, determining their targets, function and regulation. Functional miRNA studies on endocrine cancers are still scarce and represent an important area of research, since some tumors, although not frequent, present a high mortality rate. Among the endocrine tumors, thyroid cancer is the most common and best studied. Several miRNAs show lowered expression in endocrine cancers (i.e. miR-200s, miR-126, miR-7, miR-29a, miR-30a, miR-137, miR-206, miR-101, miR-613, miR-539, miR-205, miR-9, miR-195), while others are commonly overexpressed (i.e. miR-21, miR-183, miR-31, miR-let7b, miR-584, miR-146b, miR-221, miR-222, miR-25, miR-595). Additionally, some miRNAs were found in serum exosomes (miR-151, miR-145, miR-31), potentially serving as diagnostic tools. In this review, we summarize studies concerning the discovery and functions of miRNAs and their regulatory roles in endocrine cancer metastasis, which may contribute for the finding of novel therapeutic targets. The review focus on miRNAs with at least some identified targets, with established functions and, if possible, upstream regulation.

MEG3 Suppresses Human Pancreatic Neuroendocrine Tumor Cells Growth and Metastasis by Down-Regulation of Mir-183

“…Herein, we detected the cross-regulation between MEG3 and miR-183, since in a recent review, miR-183 has been reported as a pivotal miRNA in endocrine cancer metastasis [21]. Firstly, we detected the expression of miR-183 in human kidney epithelial cell line HEK293 and human pNET cell lines BON1 and QGP-1.…”

Impaired miRNA processing by DICER1 downregulation endows thyroid cancer with increased aggressiveness

“…In this regard, we and others recently profiled repressed miRs in PTC with potential tumor suppressive functions ( Cancer Genome Atlas Research Network, 2014;Riesco-Eizaguirre et al, 2015), which included miR-30a and miR-100. These miRs are reported to be essential for EMT and the mesenchymal phenotype by, for example, targeting lysyl oxidase and promoting SNAIL2 expression (Boufraqech et al, 2015;Hebrant et al, 2014;Lima et al, 2017) or have been described as tumor suppressors in other cancer entities. To assess whether the effects of DICER1 silencing are directly attributed to these repressed miRs, we restored miR-30a and miR-100 expression in DICER1-silenced cells and monitored the resulting phenotype.…”

Inhibition of <i>miR-183</i> Induces Insulin in Dental Pulp Cells

“…These results suggest that the direct conversion of dental pulp cells into the cells of developmentally unrelated tissues involves miRNA-dependent regulation. Recently, some reports show that miR-183 is detectable in human serum, urine, and in exosome vesicles from human sera and is involved in endocrine-associated signal transduction [16][17][18] . Given that miRNAs, including miR-183, work as a cluster, it remains unclear whether miR-183 is the only major miRNA involved in this process.…”