MicroRNAs as Biomarkers in Thyroid Carcinoma

Celano, Marilena; Rosignolo, Francesca; Maggisano, Valentina; Pecce, Valeria; Iannone, Michelangelo; Russo, Diego; Bulotta, Stefania

doi:10.1155/2017/6496570

Cited by 81 publications

(79 citation statements)

References 93 publications

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“…RET kinase activity may be important in maintaining differentiation through micro‐ribonucleic acid (miRNA) regulation. Prior work has shown the importance of miRNA in silencing target genes . RET mutations upregulate the biogenesis of miRNAs, and emerging work has identified miR30a as important in maintaining PTC differentiation through the inhibition of lysyl oxidase .…”

Section: Discussionmentioning

confidence: 99%

“…Prior work has shown the importance of miRNA in silencing target genes. 25 RET mutations upregulate the biogenesis of miRNAs, 26 and emerging work has identified miR30a as important in maintaining PTC differentiation through the inhibition of lysyl oxidase. 27,28 In addition, pAKT localization has been shown to be dependent on the presence of RET rearrangement.…”

Section: Discussionmentioning

confidence: 99%

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A molecular approach combined with American Thyroid Association classification better stratifies recurrence risk of classic histology papillary thyroid cancer

et al. 2018

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BackgroundPrognosis among patients with differentiated thyroid cancer is widely variable. Better understanding of biologic subtypes is necessary to stratify patients and improve outcomes.MethodsIn patients diagnosed with classic histology papillary thyroid cancer treated from 1973 to 2009, BRAF V600E mutation status was determined on surgical tumor specimens by restriction fragment length polymorphism analysis. A tissue microarray (TMA) was constructed from tumor specimens in triplicate and stained by immunohistochemistry for RET, phospho‐MEK, MAPK(dpERK), PPARγ, and phospho‐AKT(pAKT). Stained slides were scored independently and blindly by two investigators and compared to tumor and patient characteristics and outcomes.ResultsA total of 231 patients had archived formalin‐fixed, paraffin‐embedded tumor tissue available and were included on the TMA. Mean age at diagnosis was 44 years (range 6‐82 years); proportion of patients with female sex was (72%); 2015 American Thyroid Association (ATA) risk stratification was low (26%), intermediate (32%), and high (42%). BRAF V600E mutation was found in 74% of specimens, and IHC was scored as positive for RET (61%), MAPK (dpERK) (14%), PPARγ (27%), and pAKT (39%). Positive RET staining was associated with a lower risk of recurrence (HR = 0.46, 95% CI 0.22‐0.96). No other molecular biomarkers were independent predictors of recurrence on univariable analysis. On RPA, patients with RET‐negative and either MAPK(dpERK)‐positive or pAKT‐positive tumors were identified to have a high risk of recurrence (HR = 5.4, 95%CI 2.5‐11.7). This profile remained associated with recurrence in a multivariable model including ATA risk stratification (HR = 2.8, 95% CI 1.3‐6.0).ConclusionCharacterization of molecular pathways involved in cPTC tumorigenesis may add further risk stratification for recurrence beyond the 2015 ATA risk categories alone.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A molecular approach combined with American Thyroid Association classification better stratifies recurrence risk of classic histology papillary thyroid cancer

et al. 2018

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“…Total RNA and small RNA quality control was by Fragment Analyzer (Agilent version# 1.1.0.11). qPCR was performed with 2 µL RNA input from each fraction, or from pooled fractions HMW-RISC (15)(16), MMW-RISC (17-26), LMW-RISC (27)(28)(29)(30)(31)(32)(33)(34)(35), and RISC-Poor (36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47) using TaqMan microRNA Reverse transcription kit (ABI 4366597 Lot#00636931), TaqMan miRNA stem-loop RT primers/qPCR primer probe sets (ABI 4427975) (cel-miR-39 ID# 000200 Lot#P180110-003B10, miR-16 ID# 000391 Lot#P171018-000H05, U6 ID# 001937 Lot#P170729-001405), TaqMan Universal Master Mix II, no UNG (ABI 4440040 Lot#1802074), as described in manufacturer's protocol, on a CFX96 Real-time System (Bio-Rad). For each RNA fraction, miR-16 and U6 were normalized to cel-miR-39, then to fraction 14 using the 2 -ΔΔCT method.…”

Section: Rna Extraction and Qpcrmentioning

confidence: 99%

mir-21 is associated with inactive low molecular weight Argonaute complexes in thyroid cancer cell lines

Powell

Turchinovich²,

Wang

et al. 2020

Preprint

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Thyroid cancer is the most prevalent malignancy of the endocrine system. We and others have shown that several microRNAs, which are post-transcriptional gene regulators, are aberrantly expressed in anaplastic thyroid cancer (ATC) and papillary thyroid cancer (PTC) tissues, as well as cell lines derived from these cancers. In the cell, miRNAs are bound to Argonaute (AGO) proteins as what could be termed low molecular weight RNA-Induced Silencing Complexes (LMW-RISCs) that can then assemble with additional proteins, mRNA, and translation machinery into high molecular weight RISCs (HMW-RISCs) that also exert regulatory function. In this study, we sought to analyze the association of miRNAs with RISC complexes in ATC and PTC. For ATC and PTC lines, miRNA species were enriched in both HMW-RISC and LMW-RISC cellular fractions, compared with intermediate molecular weight fractions and very low molecular weight (AGO-poor) fractions. Furthermore, 60% of all miRNAs were slightly more abundant in LMW-RISC versus HMW-RISC fractions by ~2-4 fold. Surprisingly, miR-21-5p, one of the most abundant miRNAs in both ATC and PTC lines and one of the most widely studied oncogenic miRNAs in many solid tumors, was consistently one the least abundant miRNAs in HMW-RISC and the most enriched miRNA in LMW-RISC fractions. These findings may suggest that miR-21 has a role or roles distinct from canonical posttranscriptional regulation in cancer. Furthermore, the methodology described here is a useful way to assess the distribution of miR-21 between HMW and LMW-RISCs and may help to reveal the true roles of this miRNA in thyroid cancer development, progression, and treatment.

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“…6 Through complementary binding to 3' untranslated regions (3′UTR), miRNAs exhibit suppressive impacts on gene expression. 6 Through complementary binding to 3' untranslated regions (3′UTR), miRNAs exhibit suppressive impacts on gene expression.…”

Section: Introductionmentioning

confidence: 99%

“…6 Through complementary binding to 3' untranslated regions (3′UTR), miRNAs exhibit suppressive impacts on gene expression. 6 The implication of miRNAs in cancers has been increasingly documented, 8,9 including in thyroid cancer. 6 The implication of miRNAs in cancers has been increasingly documented, 8,9 including in thyroid cancer.…”

Section: Introductionmentioning

confidence: 99%

miR‐4319 inhibited the development of thyroid cancer by modulating FUS‐stabilized SMURF1

Bian

2019

J of Cellular Biochemistry

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Thyroid cancer, a common type of endocrine system cancer, has witnessed rising incidence and deaths over the past few years. The role of microRNAs is being increasingly discovered in a variety of cancers, including thyroid cancer. miR‐4319 has been elucidated in several studies to exert an antitumor function in multiple cancers but has never been explored in thyroid cancer. Our study proposed to explore the function and modulatory mechanism of miR‐4319 in thyroid cancer. First, we confirmed the downregulation of miR‐4319 in thyroid cancer tissues and cells, and revealed the correlation of miR‐4319 expression and clinical features in thyroid cancer. Functional assays illustrated that miR‐4319 attenuated proliferation, migration, and epithelial‐to‐mesenchymal transition (EMT) in thyroid cancer. Mechanistically, we identified through the miRDB database and proved that miR‐4319 targeted SMAD specific E3 ubiquitin protein ligase 1 (SMURF1). Furthermore, we discovered that miR‐4319 competed with fused in sarcoma (FUS) to bind to SMURF1, inhibiting the stabilization of SMURF1 messenger RNA. Rescue assays suggested that miR‐4319 retarded proliferation, migration, and EMT through SMURF1. Collectively, the results of this study showed that miR‐4319 inhibited the development of thyroid cancer by modulating FUS‐stabilized SMURF1, indicating miR‐4319 as a potent biological target for thyroid cancer.

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MicroRNAs as Biomarkers in Thyroid Carcinoma

Cited by 81 publications

References 93 publications

A molecular approach combined with American Thyroid Association classification better stratifies recurrence risk of classic histology papillary thyroid cancer

A molecular approach combined with American Thyroid Association classification better stratifies recurrence risk of classic histology papillary thyroid cancer

mir-21 is associated with inactive low molecular weight Argonaute complexes in thyroid cancer cell lines

miR‐4319 inhibited the development of thyroid cancer by modulating FUS‐stabilized SMURF1

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