MicroRNAs in thyroid development, function and tumorigenesis

“…Thus, unbalanced miRNA expression is involved in the pathogenesis of human diseases, including cancer, for which unbalanced miRNA acts in an oncogenic or tumor-suppressive fashion. In terms of bioinformatics, miRNAs regulate more than 60% of protein-coding genes' mRNAs (based on miRNA seed-sequence conservation) (12); this indicates that these noncoding RNAs could regulate all cellular processes, including thyroid-cell differentiation and tumorigenesis (7,15).…”

Section: Microrna and Thyroid Follicular Cell Differentiationmentioning

confidence: 99%

Interplay of TGFβ signaling and microRNA in thyroid cell loss of differentiation and cancer progression

Fuziwara

Saito

Kimura

2019

Archives of Endocrinology and Metabolism

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Thyroid cancer has been rapidly increasing in prevalence among humans in last 2 decades and is the most prevalent endocrine malignancy. Overall, thyroid-cancer patients have good rates of long-term survival, but a small percentage present poor outcome. Thyroid cancer aggressiveness is essentially related with thyroid follicular cell loss of differentiation and metastasis. The discovery of oncogenes that drive thyroid cancer (such as RET, RAS, and BRAF), and are aligned in the MAPK/ERK pathway has led to a new perspective of thyroid oncogenesis. The uncovering of additional oncogenemodulated signaling pathways revealed an intricate and active signaling cross-talk. Among these, microRNAs, which are a class of small, noncoding RNAs, expanded this cross-talk by modulating several components of the oncogenic network-thus establishing a new layer of regulation. In this context, TGFβ signaling plays an important role in cancer as a dual factor: it can exert an antimitogenic effect in normal thyroid follicular cells, and promote epithelial-to-mesenchymal transition (EMT), cell migration, and invasion in cancer cells. In this review, we explore how microRNAs influence the loss of thyroid differentiation and the increase in aggressiveness of thyroid cancers by regulating the dual function of TGFβ. This review provides directions for future research to encourage the development of new strategies and molecular approaches that can improve the treatment of aggressive thyroid cancer.

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“…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.…”

mentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

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

Jackson

Kumar

Banizs

et al. 2019

Diagnostic Cytopathology

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INTRODUCTION: Focused and expanded mutation panels were assessed for the incremental utility of using an expanded panel in combination with microRNA risk classification. METHODS: Molecular results were reviewed for patients who underwent either a focused mutation panel (ThyGenX ® ) or an expanded mutation panel (ThyGeNEXT ® ) for strong and weak oncogenic driver mutations and fusions. microRNA results (ThyraMIR ® ) predictive of malignancy, including strong positive results highly specific for malignancy, were examined. RESULTS: Results of 12 993 consecutive patients were reviewed (focused panel = 8619, expanded panel = 4374). The expanded panel increased detection of strong drivers by 8% (P < .001), with BRAFV600E and TERT promoters being the most common. Strong drivers were highly correlated with positive microRNA results of which 90% were strongly positive. The expanded panel increased detection of coexisting drivers by 4% (P < .001), with TERT being the most common partner often paired with RAS. It increased the detection of weak drivers, with RAS and GNAS being the most common. 49% of nodules with weak drivers had positive microRNA results of which 33% were strongly positive. The expanded panel also decreased the number of nodules lacking mutations and fusions by 15% (P < .001), with 8% of nodules having positive microRNA results of which 22% were strongly positive.CONCLUSIONS: Using expanded mutation panels that include less common mutations and fusions can offer increased utility when used in combination with microRNA classification, which helps to identify high risk of malignancy in the cases where risk is otherwise uncertain due to the presence of only weak drivers or the absence of all drivers.

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MicroRNAs in thyroid development, function and tumorigenesis

Cited by 59 publications

References 64 publications

Familial multinodular goiter and Sertoli-Leydig cell tumors associated with a large intragenic in-frame DICER1 deletion

Familial multinodular goiter and Sertoli-Leydig cell tumors associated with a large intragenic in-frame DICER1 deletion

Interplay of TGFβ signaling and microRNA in thyroid cell loss of differentiation and cancer progression

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

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