Clinical Manifestations and Gene Expression in Patients with Conventional Papillary Thyroid Carcinoma Carrying the BRAFV600E Mutation and BRAF Pseudogene

Lin, Jiunn‐Diann; Fu, Shuai; Chen, Jui Yu; Lee, Chen Hsen; Chau, Wing‐Keung; Cheng, Chao‐Wen; Wang, Yuan–Hung; Lin, Yuh‐Feng; Fang, Wen; Tang, Kuo‐Tung

doi:10.1089/thy.2015.0044

Cited by 18 publications

(13 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar to the literature, mutually exclusive somatic alterations were found in BRAF (68% of PTC samples) and RET (12%), while RAS had no mutations [18, 45, 46]. The supervised clustering analysis of the methylation profiling revealed six PTC grouped with NT samples, two of them were BRAF V600E and one RET-PTC 3 positive.…”

Section: Discussionsupporting

confidence: 77%

Integrated data analysis reveals potential drivers and pathways disrupted by DNA methylation in papillary thyroid carcinomas

et al. 2017

View full text Add to dashboard Cite

BackgroundPapillary thyroid carcinoma (PTC) is a common endocrine neoplasm with a recent increase in incidence in many countries. Although PTC has been explored by gene expression and DNA methylation studies, the regulatory mechanisms of the methylation on the gene expression was poorly clarified. In this study, DNA methylation profile (Illumina HumanMethylation 450K) of 41 PTC paired with non-neoplastic adjacent tissues (NT) was carried out to identify and contribute to the elucidation of the role of novel genic and intergenic regions beyond those described in the promoter and CpG islands (CGI). An integrative and cross-validation analysis were performed aiming to identify molecular drivers and pathways that are PTC-related.ResultsThe comparisons between PTC and NT revealed 4995 methylated probes (88% hypomethylated in PTC) and 1446 differentially expressed transcripts cross-validated by the The Cancer Genome Atlas data. The majority of these probes was found in non-promoters regions, distant from CGI and enriched by enhancers. The integrative analysis between gene expression and DNA methylation revealed 185 and 38 genes (mainly in the promoter and body regions, respectively) with negative and positive correlation, respectively. Genes showing negative correlation underlined FGF and retinoic acid signaling as critical canonical pathways disrupted by DNA methylation in PTC. BRAF mutation was detected in 68% (28 of 41) of the tumors, which presented a higher level of demethylation (95% hypomethylated probes) compared with BRAF wild-type tumors. A similar integrative analysis uncovered 40 of 254 differentially expressed genes, which are potentially regulated by DNA methylation in BRAFV600E-positive tumors. The methylation and expression pattern of six selected genes (ERBB3, FGF1, FGFR2, GABRB2, HMGA2, and RDH5) were confirmed as altered by pyrosequencing and RT-qPCR.ConclusionsDNA methylation loss in non-promoter, poor CGI and enhancer-enriched regions was a significant event in PTC, especially in tumors harboring BRAFV600E. In addition to the promoter region, gene body and 3’UTR methylation have also the potential to influence the gene expression levels (both, repressing and inducing). The integrative analysis revealed genes potentially regulated by DNA methylation pointing out potential drivers and biomarkers related to PTC development.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-017-0346-2) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionsupporting

confidence: 77%

Integrated data analysis reveals potential drivers and pathways disrupted by DNA methylation in papillary thyroid carcinomas

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Evidently, like the parent gene BRAF, BRAF pseudogene plays an oncogenic role by activating the MAP kinase signaling pathway, leading to the formation of tumors in nude mice. However, a recent study suggests that BRAF pseudogene mRNA levels are positively correlated with BRAF mRNA levels [ 69 ], which could be through ceRNA mechanism.…”

Section: Role Of Pseudogenes In Cancermentioning

confidence: 99%

Role of Pseudogenes in Tumorigenesis

Yang

2018

Cancers

View full text Add to dashboard Cite

Functional genomics has provided evidence that the human genome transcribes a large number of non-coding genes in addition to protein-coding genes, including microRNAs and long non-coding RNAs (lncRNAs). Among the group of lncRNAs are pseudogenes that have not been paid attention in the past, compared to other members of lncRNAs. However, increasing evidence points the important role of pseudogenes in diverse cellular functions, and dysregulation of pseudogenes are often associated with various human diseases including cancer. Like other types of lncRNAs, pseudogenes can also function as master regulators for gene expression and thus, they can play a critical role in various aspects of tumorigenesis. In this review we discuss the latest developments in pseudogene research, focusing on how pseudogenes impact tumorigenesis through different gene regulation mechanisms. Given the high sequence homology with the corresponding parent genes, we also discuss challenges for pseudogene research.

show abstract

Section: Introductionmentioning

confidence: 99%

“…Pseudogenes can regulate gene expression at multiple levels, and are involved in various biological processes, including cancer development and progression ( 9 ). The BRAF pseudogene has been shown to act as a competing endogenous RNA (ceRNA) in lymphoma ( 10 ). Additionally, other studies have demonstrated that both pituitary tumor-transforming 3 pseudogene and protein disulfide isomerase family A member 3 pseudogene 1 are upregulated in hepatocellular carcinoma ( 11 , 12 ), while double homeobox A pseudogene (DUXAP) 8 promotes non-small cell lung cancer (NSCLC) cell proliferation and invasiveness ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

Pseudogene legumain promotes thyroid carcinoma progression via the microRNA‑495/autophagy pathway

et al. 2021

View full text Add to dashboard Cite

The pseudogene legumain (LGMN) has been reported to regulate cancer cell biology. However, the role of LGMN in thyroid carcinoma remains unknown. Herein, Cell Counting Kit 8 and Transwell assays were performed to evaluate cellular proliferation and invasion capacity, respectively. In addition, a tube formation assay was performed to assess HUVEC angiogenesis. The results showed that LGMN depletion attenuated cellular proliferation, invasion and tube formation ability, and that LGMN expression was dysregulated in thyroid carcinoma tumors. Furthermore, patients with high LGMN expression levels exhibited a lower overall survival rate than those with low expression levels. LGMN and microRNA (miR)-495 modulated the expression levels of autophagy-related gene 3 (ATG3) and p62. Finally, ATG3 overexpression rescued the LGMN-regulated thyroid carcinoma phenotype. In conclusion, LGMN was found to promote thyroid carcinoma progression via the miR-495/autophagy axis, thus providing novel insights for understanding the pathogenesis of thyroid carcinoma.

show abstract

Clinical Manifestations and Gene Expression in Patients with Conventional Papillary Thyroid Carcinoma Carrying the BRAF^V600E Mutation and BRAF Pseudogene

Cited by 18 publications

References 45 publications

Integrated data analysis reveals potential drivers and pathways disrupted by DNA methylation in papillary thyroid carcinomas

Integrated data analysis reveals potential drivers and pathways disrupted by DNA methylation in papillary thyroid carcinomas

Role of Pseudogenes in Tumorigenesis

Pseudogene legumain promotes thyroid carcinoma progression via the microRNA‑495/autophagy pathway

Contact Info

Product

Resources

About