TERT Promoter Mutated Follicular Thyroid Carcinomas Exhibit a Distinct microRNA Expressional Profile with Potential Implications for Tumor Progression

Paulsson, Johan O.; Zedenius, Jan; Juhlin, C. Christofer

doi:10.1007/s12022-021-09695-w

Cited by 6 publications

(7 citation statements)

References 10 publications

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“…We obtained similar results; however, we report that FTC change in expression is only significant when compared to FTAs but not NTAT. Aberrant expression of miRNA biosynthesis genes DGCR8 and DROSHA are described to promote tumorigenesis as it results in aberrant miRNA expressional pattern that could be at play even at the level of tumour initiation, by downregulating tumour suppressor genes or overexpressing oncogenes [ 21 , 27 ]. These results suggest that overexpression of DGCR8 , especially in FTA (the highest DGCR8 expression), could be at play to force maintenance of “normal” thyroid differentiation, in particular, of the follicular differentiation and structure.…”

Section: Discussionmentioning

confidence: 99%

“…A dependence of DGCR8 in follicular-patterned carcinomas, already described by Paulsson et al [ 21 ], is reported in this study with a statistical significative DGCR8 mRNA underexpression in follicular-patterned carcinomas (FTC and FV-PTC) when compared to the normal counterpart. Beyond DGCR8 , somatic DICER1 mutations are reported in follicular-patterned lesions of thyroid (benign and malignant) which underlines the importance of the miRNA processing genes in follicular-patterned lesions [ 27 , 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

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DGCR8 Microprocessor Subunit Mutation and Expression Deregulation in Thyroid Lesions

Rodrigues

Canberk

Macedo

et al. 2022

IJMS

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DGCR8 emerged recently as miRNAs biogenesis pathway protein with a highlighted role in thyroid disease. This study aimed to characterize this miRNA biogenesis component, in particular the p.(E518K) mutation and DGCR8 expression in a series of thyroid lesions. The series of thyroid lesions was genotyped for the c.1552G>A p.(E518K) mutation. When frozen tissue was available, DGCR8 mRNA expression was analysed by qPCR. Formalin-fixed paraffin-embedded tissues were studied for DGCR8 immunoexpression. We present for the first time the p.(E518K) mutation in a case of poorly differentiated thyroid carcinoma and present the deregulation of DGCR8 expression at mRNA level in follicular-patterned tumours. The obtained data solidify DGCR8 as another important player of miRNA-related gene mutations in thyroid tumorigenesis, particularly in follicular-patterned thyroid tumours.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

DGCR8 Microprocessor Subunit Mutation and Expression Deregulation in Thyroid Lesions

Rodrigues

Canberk

Macedo

et al. 2022

IJMS

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“…However, RAS gene mutations can occur in both malignant and benign thyroid nodules, and the use of RAS alone in the differential diagnosis of benign and malignant thyroid nodules and the assessment of prognosis has limitations. Recent studies have found that TERT promoter mutation is closely related to high tumor aggressiveness, and TERT promoter mutated FTCs may exhibit a specific miRNA pattern that in part regulates key cancer pathways ( 14 – 16 ). Detection of the BRAF, RAS and TERT promoters is helpful for evaluating and predicting the biological behavior of thyroid cancer ( 17 , 18 ).…”

Section: Discussionmentioning

confidence: 99%

Case report: Large follicular thyroid carcinoma with multiple cervical lymph node metastases

Liao

Tan

et al. 2022

Front. Surg.

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IntroductionFollicular thyroid carcinoma (FTC) rarely metastasizes to regional lymph nodes, as they mainly metastasize through hematogenous route; in particular, a large FTC with only lateral lymph node metastasis and without distant metastasis has rarely been reported.Case reportWe present a 66-year-old male patient with a progressively growing thyroid for more than 20 years, causing tracheal compression and narrowing. Neck ultrasonography, computed tomography (CT), magnetic resonance (MR) imaging and positron emission tomography–computed tomography (PET/CT) were carried out to obtain images of the thyroid and surrounding tissues. Total thyroidectomy and cervical lateral and central lymph node dissection were undertaken, and histopathological, and immunohistochemical evaluations and molecular pathology confirmed the diagnosis of FTC with multiple cervical lymph node metastases.ConclusionWe have reported a rare case of large FTC with diffuse nodal involvement but no distant metastases. We present the thyroid ultrasound, neck CT, MR and whole body PET/CT.

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“… 31 It has been reported that TERT promoter mutated follicular thyroid carcinomas exhibit a distinct miRNA expressional profile. 32 Additionally, it has been reported that ncRNA can regulate TERT expression in cancer; however, it is still unclear whether TERT promoter mutations can influence ncRNA regulation. 29 The evidence indicates that ncRNA might be a novel prospect of TERT promoter mutation research in HCC.…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis of Altered lncRNA, circRNA, microRNA, and mRNA Expression in Hepatocellular Carcinoma Carrying TERT Promoter Mutations

Zhang¹,

Zhang²,

Yu³

2022

JHC

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Background and Objectives Telomerase reverse transcriptase (TERT) promoter mutations are one of the most common mutations responsible for the development of hepatocellular carcinoma (HCC). Noncoding RNAs (ncRNAs) play a regulatory role in different cancers through the long noncoding RNA (lncRNA)/circular RNA (circRNA)-microRNA (miRNA)-mRNA axis. The aim of the study was to explore the influence of TERT promoter mutations on the ncRNA regulatory network in HCC. Methods Four tumor samples with a wildtype TERT promoter and four tumor samples with TERT promoter mutations (sequencing cohort) were collected from HCC patients for high-throughput next-generation sequencing. Selected ncRNAs and mRNAs were validated by qPCR in 15 HCC tumors with a wildtype TERT promoter and seven HCC tumors with TERT promoter mutations (validation cohort, including the sequencing cohort). Results In the mutant TERT promoter group, 536 lncRNAs, 21 circRNAs, 41 miRNAs, and 266 mRNAs were significantly up-regulated, while 1745 lncRNAs, 23 circRNAs, 32 miRNAs, and 1117 mRNAs were significantly down-regulated ( P < 0.05) compared with the findings in wildtype group. AL360169.3-201, LINC02672-203, hsa_circ_0021412, hsa-miR-29b-1-5p, hsa-miR-4699-5p, hsa-miR-199a-5p, REG3A, SFRP5, and GSTM1 were verified at the RNA expression level to validate the sequencing results. A differentially expressed lncRNA/circRNA-miRNA-mRNA network was constructed to explore the effects of TERT promoter mutations on ncRNA regulation. Two ncRNA regulatory axes associated with TERT promoter mutations (hsa_circ_0003154/hsa_circ_0008952/IGLL5-AS1/LINC576/LINC575–hsa-miR-1260b –CLPTM1L/GSTM1 and hsa_circ_0031584/LINC2101–hsa-miR-214-3p–CD151) had carcinogenic potential. Conclusion This study provides novel insights into the role of TERT promoter mutations on ncRNAs regulatory network in HCC progression.

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TERT Promoter Mutated Follicular Thyroid Carcinomas Exhibit a Distinct microRNA Expressional Profile with Potential Implications for Tumor Progression

Cited by 6 publications

References 10 publications

DGCR8 Microprocessor Subunit Mutation and Expression Deregulation in Thyroid Lesions

DGCR8 Microprocessor Subunit Mutation and Expression Deregulation in Thyroid Lesions

Case report: Large follicular thyroid carcinoma with multiple cervical lymph node metastases

Integrated Analysis of Altered lncRNA, circRNA, microRNA, and mRNA Expression in Hepatocellular Carcinoma Carrying TERT Promoter Mutations

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