Differences in miRNA expression profiles between wild-type and mutated NIFTPs

Denaro, Maria; Ugolini, Clara; Poma, Anello Marcello; Borrelli, Nicla; Materazzi, Gabriele; Piaggi, Paolo; Chiarugi, Massimo; Miccoli, Paolo; Vitti, Paolo; Basolo, Fulvio

doi:10.1530/erc-17-0167

Cited by 17 publications

(14 citation statements)

References 47 publications

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“…Molecular analysis cannot accurately differentiate these tumors because NIFTPs have molecular profiles similar to those of FA and IEFVPTC, with frequent RAS-like mutations [21][22][23]. However, recent studies have shown the miRNA expression profiles of NIFTPs to be different from those of other thyroid tumors [24,25].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA Profile for Diagnostic and Prognostic Biomarkers in Thyroid Cancer

Park

Kim

Jeon

et al. 2021

Cancers

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The challenge in managing thyroid nodules is to accurately diagnose the minority of those with malignancy. We aimed to identify diagnostic and prognostic miRNA markers for thyroid nodules. In a discovery cohort, we identified 20 candidate miRNAs to differentiate between noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) and papillary thyroid carcinomas (PTC) by using the high-throughput small RNA sequencing method. We then selected three miRNAs (miR-136, miR-21, and miR-127) that were differentially expressed between the PTC follicular variant and other variants in The Cancer Genome Atlas data. High expression of three miRNAs differentiated thyroid cancer from nonmalignant tumors, with an area under curve (AUC) of 0.76–0.81 in an independent cohort. In patients with differentiated thyroid cancer, the high-level expression of the three miRNAs was an independent indicator for both distant metastases and recurrent or persistent disease. In patients with PTC, a high expression of miRNAs was associated with an aggressive histologic variant, extrathyroidal extension, distant metastasis, or recurrent or persistent disease. Three miRNAs may be used as diagnostic markers for differentiating thyroid cancers from benign tumors and tumors with extremely low malignant potential (NIFTP), as well as prognostic markers for predicting the risk of recurrent/persistent disease for differentiated thyroid cancer.

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Section: Discussionmentioning

confidence: 99%

MicroRNA Profile for Diagnostic and Prognostic Biomarkers in Thyroid Cancer

Park

Kim

Jeon

et al. 2021

Cancers

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“…miRNA-193b-3p was found to be downregulated in the renal cortices from Cd-treated animals, and downregulation of this miRNA has been shown to promote autophagy and cell survival in mouse motor neuron-like cells [ 61 ]. Additionally, downregulated miR-342-3p expression is part of a shared dysregulated miRNA expression profile in both mutated non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs) and infiltrative and invasive follicular variants of papillary thyroid carcinomas (FVPTCs); and in contrast to wild type NIFTPs, this dysregulated miRNA expression profile is predicted to promote an invasive-like phenotype by altering cell adhesion and cell migration pathways [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Cadmium Nephrotoxicity Is Associated with Altered MicroRNA Expression in the Rat Renal Cortex

Fay

Alt

Ryba

et al. 2018

Toxics

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Cadmium (Cd) is a nephrotoxic environmental pollutant that causes a generalized dysfunction of the proximal tubule characterized by polyuria and proteinuria. Even though the effects of Cd on the kidney have been well-characterized, the molecular mechanisms underlying these effects have not been fully elucidated. MicroRNAs (miRNAs) are small non-coding RNAs that regulate cellular and physiologic function by modulating gene expression at the post-transcriptional level. The goal of the present study was to determine if Cd affects renal cortex miRNA expression in a well-established animal model of Cd-induced kidney injury. Male Sprague-Dawley rats were treated with subcutaneous injections of either isotonic saline or CdCl2 (0.6 mg/kg) 5 days a week for 12 weeks. The 12-week Cd-treatment protocol resulted in kidney injury as determined by the development of polyuria and proteinuria, and a significant increase in the urinary biomarkers Kim-1, β2 microglobulin and cystatin C. Total RNA was isolated from the renal cortex of the saline control and Cd treated animals, and differentially expressed miRNAs were identified using µParafloTM microRNA microarray analysis. The microarray results demonstrated that the expression of 44 miRNAs were significantly increased and 54 miRNAs were significantly decreased in the Cd treatment group versus the saline control (t-test, p ≤ 0.05, N = 6 per group). miR-21-5p, miR-34a-5p, miR-146b-5p, miR-149-3p, miR-224-5p, miR-451-5p, miR-1949, miR-3084a-3p, and miR-3084c-3p demonstrated more abundant expression and a significant two-fold or greater increased expression in the Cd-treatment group versus the saline control group. miR-193b-3p, miR-455-3p, and miR-342-3p demonstrated more abundant expression and a significant two-fold or greater decreased expression in the Cd-treatment group versus the saline control group. Real-time PCR validation demonstrated (1) a significant (t-test, p ≤ 0.05, N = 6 per group) increase in expression in the Cd-treated group for miR-21-5p (2.7-fold), miR-34a-5p (10.8-fold), miR-146b-5p (2-fold), miR-224-5p (10.2-fold), miR-3084a-3p (2.4-fold), and miR-3084c-3p (3.3-fold) and (2) a significant (t-test, p ≤ 0.05, N = 6 per group) 52% decrease in miR-455-3p expression in the Cd-treatment group. These findings demonstrate that Cd significantly alters the miRNA expression profile in the renal cortex and raises the possibility that dysregulated miRNA expression may play a role in the pathophysiology of Cd-induced kidney injury. In addition, these findings raise the possibility that Cd-dysregulated miRNAs might be used as urinary biomarkers of Cd exposure or Cd-induced kidney injury.

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“…The expression profiling of 798 miRNAs was carried out by the nCounter human v3 miRNA expression assay (NanoString Technologies, Seattle, WA, USA), as previously described [24].…”

Section: Methodsmentioning

confidence: 99%

DICER1 somatic mutations strongly impair miRNA processing even in benign thyroid lesions

et al. 2019

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The alteration of miRNA processing is a driver event in several tumors including thyroid cancer. In particular, somatic DICER1 mutations, reported in follicular-patterned lesions, are shared by benign as well as malignant tumors. In the present study, we investigated the effects of alterations in the miRNA processing genes on the miRNA profile. The study included 19 follicular adenomas (FAs) and 22 follicular variant of papillary thyroid carcinomas (FVPTCs). The mutational status in the hot spot regions of DICER1 , DROSHA , TARBP2 , DGCR8 and the most commonly affected genes in thyroid tumors was investigated on both tumor and paired normal tissues. The miRNA profile and the mRNA expression levels of DICER1 , DROSHA , TARBP2 , DGCR8 and XPO5 were also evaluated. Two DICER1 RNase IIIb domain mutations were found in FAs. These lesions presented a considerable loss of 5p miRNAs. Fifteen miRNAs were specifically deregulated in DICER1 -mutant lesions compared to FAs and FVPTCs. These miRNAs regulate crucial pathways in cancer such as Hippo, p53 and TGF-beta signalling. DICER1 somatic mutations in the RNase IIIb domain are not specific for malignancy, but the miRNA imbalance that they cause is remarkable, especially with regard to the loss of 5p miRNAs. DICER1 -mutant lesions have a characteristic miRNA deregulation, which is different from that of FVPTCs; nevertheless, this impairment is consistent with malignant transformation. Further studies providing the real risk of malignancy associated with DICER1 mutations and the evolution of DICER1 -mutant lesions are needed to make them useful in the clinical practice.

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Differences in miRNA expression profiles between wild-type and mutated NIFTPs

Cited by 17 publications

References 47 publications

MicroRNA Profile for Diagnostic and Prognostic Biomarkers in Thyroid Cancer

MicroRNA Profile for Diagnostic and Prognostic Biomarkers in Thyroid Cancer

Cadmium Nephrotoxicity Is Associated with Altered MicroRNA Expression in the Rat Renal Cortex

DICER1 somatic mutations strongly impair miRNA processing even in benign thyroid lesions

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