Identification of Long Noncoding RNAs Deregulated in Papillary Thyroid Cancer and Correlated with BRAFV600E Mutation by Bioinformatics Integrative Analysis

Goedert, Lucas; Plaça, Jéssica Rodrigues; Fuziwara, César Seigi; Machado, Maiaro Cabral Rosa; Plaça, Desireé Rodrigues; Almeida, Palloma Porto; Sanches, Talita Perez; Santos, Jair Figueredo dos; Corveloni, Amanda Cristina; Pereira, Illy Enne Gomes; Castro, Marcela Motta de; Kimura, Edna Teruko; Silva, Wilson A.; Espreáfico, Enilza Maria

doi:10.1038/s41598-017-01957-0

Cited by 29 publications

(21 citation statements)

References 60 publications

(86 reference statements)

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“…For the results of the pathway analysis in this study, we consulted the literature and retrieved more relevant information. ECM-receptor interactions have been found to play a role in the development of papillary thyroid carcinoma [38]. Activation of the p53 signaling pathway could induce In addition, we used the CMap database to find small molecules of drugs that might reverse the expression of thyroid cancer genes.…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Biomarkers for Thyroid Cancer Using Bioinformatics Strategy: A Study Based on GEO Datasets

Shen

Dong

Liu

et al. 2020

BioMed Research International

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Background. The molecular mechanisms and genetic markers of thyroid cancer are unclear. In this study, we used bioinformatics to screen for key genes and pathways associated with thyroid cancer development and to reveal its potential molecular mechanisms. Methods. The GSE3467, GSE3678, GSE33630, and GSE53157 expression profiles downloaded from the Gene Expression Omnibus database (GEO) contained a total of 164 tissue samples (64 normal thyroid tissue samples and 100 thyroid cancer samples). The four datasets were integrated and analyzed by the RobustRankAggreg (RRA) method to obtain differentially expressed genes (DEGs). Using these DEGs, we performed gene ontology (GO) functional annotation, pathway analysis, protein-protein interaction (PPI) analysis and survival analysis. Then, CMap was used to identify the candidate small molecules that might reverse thyroid cancer gene expression. Results. By integrating the four datasets, 330 DEGs, including 154 upregulated and 176 downregulated genes, were identified. GO analysis showed that the upregulated genes were mainly involved in extracellular region, extracellular exosome, and heparin binding. The downregulated genes were mainly concentrated in thyroid hormone generation and proteinaceous extracellular matrix. Pathway analysis showed that the upregulated DEGs were mainly attached to ECM-receptor interaction, p53 signaling pathway, and TGF-beta signaling pathway. Downregulation of DEGs was mainly involved in tyrosine metabolism, mineral absorption, and thyroxine biosynthesis. Among the top 30 hub genes obtained in PPI network, the expression levels of FN1, NMU, CHRDL1, GNAI1, ITGA2, GNA14 and AVPR1A were associated with the prognosis of thyroid cancer. Finally, four small molecules that could reverse the gene expression induced by thyroid cancer, namely ikarugamycin, adrenosterone, hexamethonium bromide and clofazimine, were obtained in the CMap database. Conclusion. The identification of the key genes and pathways enhances the understanding of the molecular mechanisms for thyroid cancer. In addition, these key genes may be potential therapeutic targets and biomarkers for the treatment of thyroid cancer.

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Section: Discussionmentioning

confidence: 99%

Identification of Potential Biomarkers for Thyroid Cancer Using Bioinformatics Strategy: A Study Based on GEO Datasets

Shen

Dong

Liu

et al. 2020

BioMed Research International

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“…Non-coding RNAs can have regulatory functions to diversify the genetic output and, due to their high stability and association with the pathogenesis of human cancers, are promising diagnostic and prognostic biomarkers 19 - 21 . They may also function to amplify the malignancy and progression of cancer induced by other genomic alterations 70 . Although several lncRNAs are aberrantly expressed in PTC 23 - 27 , their key targets have not yet been identified.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic signature associated with carcinogenesis and aggressiveness of papillary thyroid carcinoma

et al. 2018

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Papillary thyroid carcinoma (PTC) is the fastest-growing disease caused by numerous molecular alterations in addition to previously reported DNA mutations. There is a compelling need to identify novel transcriptomic alterations that are associated with the pathogenesis of PTC with potential diagnostic and prognostic implications.Methods: We gathered and compared 242 expression profiles between paired PTC and adjacent normal tissues and identified and validated the coding and long non-coding RNAs (lncRNAs) associated with the extrathyroidal extension (ETE) of 655 PTC patients in two independent cohorts, followed by predicting their interactions with drugs. Co-expression, RNA interaction, Kaplan-Meier survival and multivariate Cox proportional regression analyses were performed to identify dysregulated lncRNAs and genes that correlated with clinical outcomes of PTC. Alternative splicing (AS), RNA circularization, and editing were also compared between transcriptomes to expand the repertoire of molecular alterations in PTC.Results: Numerous genes related to cellular microenvironment and steroid hormone response were associated with the ETE of PTC. Drug susceptibility predictions of the expression signature revealed two highly ranked compounds, 6-bromoindirubin-3'-oxime and lovastatin. Co-expression and RNA interaction analysis revealed the essential role of lncRNAs in PTC pathogenesis by modulating extracellular matrix and cell adhesion. Eight genes and two novel lncRNAs were identified that correlated with the aggressive nature and disease-free survival of PTC. Furthermore, this study provided the transcriptome-wide landscape of circRNAs in PTC and uncovered dissimilar expression profiles among circRNAs originating from the same host gene, suggesting the functional complexity of circRNAs in PTC carcinogenesis. The newly identified AS events in the SERPINA1 and FN1 genes may improve the sensitivity and specificity of these diagnostic biomarkers.Conclusions: Our study uncovered a comprehensive transcriptomic signature associated with the carcinogenesis and aggressive behavior of PTC, as well as presents a catalog of 10 potential biomarkers, which would facilitate PTC prognosis and development of new therapeutic strategies for this cancer.

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“…Numerous studies have reported that, as members of noncoding RNAs (ncRNAs), microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) play essential roles in regulating the pathologic network of PTC in different stages . LncRNAs are defined as a cluster of transcripts with more than 200 nucleotides without protein‐coding potential, which were originally considered as transcriptional noise.…”

Section: Introductionmentioning

confidence: 99%

Retracted: LINC00311 promotes cancer stem‐like properties by targeting miR‐330‐5p/TLR4 pathway in human papillary thyroid cancer

et al. 2020

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Growing evidence has suggested that long noncoding RNAs (lncRNAs) play an essential role in the progression of papillary thyroid cancer (PTC). LncRNA LINC00311 was found to be able to regulate many cellular process in several diseases. However, the function and regulatory mechanism of LINC00311 remains unclear in PTC. In the present study, the results showed that the expression of LINC00311 was upregulated in PTC tissues and cells. Furthermore, knockdown of LINC00311 dramatically suppressed spheroid formation, proliferation, migration, and invasion in PTC cells in vitro. Mechanistic investigations revealed that LINC00311 was negatively correlated with the expression of miR‐330‐5p, meanwhile, TLR4 was a direct target of miR‐330‐5p. In addition, rescue assays further determined that LINC00311 contributed to the progression of PTC through regulating TLR4 expression. Taken together, these findings indicated that LINC00311 could promote cancer stem‐like properties by targeting miR‐330‐5p/TLR4 pathway in PTC.

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Identification of Long Noncoding RNAs Deregulated in Papillary Thyroid Cancer and Correlated with BRAFV600E Mutation by Bioinformatics Integrative Analysis

Cited by 29 publications

References 60 publications

Identification of Potential Biomarkers for Thyroid Cancer Using Bioinformatics Strategy: A Study Based on GEO Datasets

Identification of Potential Biomarkers for Thyroid Cancer Using Bioinformatics Strategy: A Study Based on GEO Datasets

Transcriptomic signature associated with carcinogenesis and aggressiveness of papillary thyroid carcinoma

Retracted: LINC00311 promotes cancer stem‐like properties by targeting miR‐330‐5p/TLR4 pathway in human papillary thyroid cancer

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