miRNA expression and function in thyroid carcinomas: a comparative and critical analysis and a model for other cancers

Abstract

As in many cancer types, miRNA expression profiles and functions have become an important field of research on non-medullary thyroid carcinomas, the most common endocrine cancers. This could lead to the establishment of new diagnostic tests and new cancer therapies. However, different studies showed important variations in their research strategies and results. In addition, the action of miRNAs is poorly considered as a whole because of the use of underlying dogmatic truncated concepts. These lead to discrepancies and limits rarely considered. Recently, this field has been enlarged by new miRNA functional and expression studies. Moreover, studies using next generation sequencing give a new view of general miRNA differential expression profiles of papillary thyroid carcinoma. We analyzed in detail this literature from both physiological and differential expression points of view. Based on explicit examples, we reviewed the progresses but also the discrepancies and limits trying to provide a critical approach of where this literature may lead. We also provide recommendations for future studies. The conclusions of this systematic analysis could be extended to other cancer types.

Incremental utility of expanded mutation panel when used in combination with microRNA classification in indeterminate thyroid nodules

“…15,26,27 Although PIK3CA and PTEN mutations have been reported in follicular thyroid cancer, poorly differentiated thyroid cancers, and anaplastic thyroid cancer, [28][29][30] they can also be found in benign thyroid adenomas, as can GNAS and ALK mutations and THADA-and PPARG-related fusions. [46][47][48][49][50] A multiplatform approach using a combination of a mutation panel and a microRNA risk classifier has been shown to effectively "rule-in" and "rule-out" high risk of malignancy with results being predictive of surgical treatment decisions that are appropriately aligned with cancer risk. 15 Although the predictive value for malignancy of these oncogenic changes is not well understood when found individually, it is well established that coexistence of many of these oncogenic changes along with other oncogenic drivers is generally associated with aggressive forms of thyroid cancer and poor prognosis.…”

“…In contrast to mutations and fusions that occur at the intracellular level, microRNAs are uniquely designed to travel from one cell to another, regulating intercellular communication across multiple pathways, which places them central to understanding the transition from pre-cancer states through malignant transformation and spread of cancers. [46][47][48][49][50] A multiplatform approach using a combination of a mutation panel and a microRNA risk classifier has been shown to effectively "rule-in" and "rule-out" high risk of malignancy with results being predictive of surgical treatment decisions that are appropriately aligned with cancer risk. 6,51,52 Furthermore, microRNA risk classification has been shown to help to reclassify cancer risk in both the absence of mutational change and the presence of mutations that have lower positive predictive values for malignancy, with strong positive microRNA classifier results offering extremely high specificity for malignancy.…”

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

“…We have demonstrated that global miR downregulation induced by DICER1 promotes thyroid cell aggressiveness. Noteworthy, thyroid cancer progression leads to less upregulated and more downregulated miRs (Hebrant et al, 2014;Saiselet et al, 2016).…”

“…However, little is known about the underlying mechanisms and the phenotypic advantages provided to cells by reduced miR expression. Interestingly, in thyroid cancer, differentiated PTC and FTC present both up-and down-regulated miRs, whereas dedifferentiated and aggressive ATC show almost exclusively down-regulated miRs, with various reports describing 44 down-regulated miRNAs and only 6 up-regulated miRNAs (Braun et al, 2010;Hebrant et al, 2014;Saiselet et al, 2016). This suggests that the progression of differentiated thyroid carcinomas to aggressive ATC is characterized by dramatic changes in miR expression, and that miR downregulation might play a role in this transition.…”

Construction and analyses of the microRNA-target gene differential regulatory network in thyroid carcinoma

“…Recent studies have emphasized the role of miRNA in THCA development [9]. Hong et al found that miR-20b functioned as a tumor-suppressor in THCA by regulating the MAPK/ERK signaling pathway [10].…”