In silico identification of novel non-synonymous variants in metabolic pathway associated target genes of papillary thyroid carcinoma: A way towards future treatment of papillary thyroid carcinoma

Meta Gene ◽  
2020 ◽  
Vol 24 ◽  
pp. 100700
Author(s):  
Manisha Ray ◽  
Saurav Sarkar
Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3304
Author(s):  
Sara Mellid ◽  
Javier Coloma ◽  
Bruna Calsina ◽  
María Monteagudo ◽  
Juan M. Roldán-Romero ◽  
...  

Over the past few years, next generation technologies have been applied to unravel the genetics of rare inherited diseases, facilitating the discovery of new susceptibility genes. We recently found germline DNMT3A gain-of-function variants in two patients with head and neck paragangliomas causing a characteristic hypermethylated DNA profile. Here, whole-exome sequencing identifies a novel germline DNMT3A variant (p.Gly332Arg) in a patient with bilateral carotid paragangliomas, papillary thyroid carcinoma and idiopathic intellectual disability. The variant, located in the Pro-Trp-Trp-Pro (PWWP) domain of the protein involved in chromatin targeting, affects a residue mutated in papillary thyroid tumors and located between the two residues found mutated in microcephalic dwarfism patients. Structural modelling of the variant in the DNMT3A PWWP domain predicts that the interaction with H3K36me3 will be altered. An increased methylation of DNMT3A target genes, compatible with a gain-of-function effect of the alteration, was observed in saliva DNA from the proband and in one independent acute myeloid leukemia sample carrying the same p.Gly332Arg variant. Although further studies are needed to support a causal role of DNMT3A variants in paraganglioma, the description of a new DNMT3A alteration in a patient with multiple clinical features suggests a heterogeneous phenotypic spectrum related to DNMT3A germline variants.


2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Jing Zeng ◽  
Xiao Ma ◽  
Jinjing Wang ◽  
Ran Liu ◽  
Yun Shao ◽  
...  

Abstract Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Hydroxysteroid dehydrogenase like 2 (HSDL2) can regulate lipid metabolism and take part in cell proliferation. The purpose of the present study was to explore functional role of HSDL2 gene in PTC. The expression of HSDL2 protein in PTC tissues was estimated using immunohistochemistry analysis (IHC). HSDL2 mRNA level was detected through quantitative real-time polymerase chain reaction (qRT-PCR). Effects of HSDL2 gene on cell proliferation and apoptosis were assessed using the shRNA method for both in vitro and in vivo experiments. Potential target genes of HSDL2 were determined via bioinformatics analyses and Western blotting. HSDL2 was up-regulated in PTC tissues and cell lines compared with the controls (all P<0.05). Inhibiting HSDL expression could suppress PTC cell proliferation and cycle, and promote apoptosis in vitro. In vivo, the knockdown of HSDL2 gene could significantly suppress tumor growth (all P<0.05). Furthermore, AKT3, NFATc2 and PPP3CA genes might be potential targets of HSDL2 in PTC. HSDL2 expression was increased in PTC tissues and cells, which could promote tumor progression in vitro and in vivo.


PLoS ONE ◽  
2016 ◽  
Vol 11 (6) ◽  
pp. e0156658 ◽  
Author(s):  
Francesca Rosignolo ◽  
Marialuisa Sponziello ◽  
Cosimo Durante ◽  
Cinzia Puppin ◽  
Catia Mio ◽  
...  

Author(s):  
Ana Paula Santin Bertoni ◽  
Patrícia de Araujo Manfroi ◽  
Joelson Tomedi ◽  
Beatriz Maria Assis-Brasil ◽  
Erika Laurini de Souza Meyer ◽  
...  

Medicine ◽  
2018 ◽  
Vol 97 (51) ◽  
pp. e13802 ◽  
Author(s):  
Fada Xia ◽  
Bo Jiang ◽  
Yong Chen ◽  
Xin Du ◽  
Yao Peng ◽  
...  

2020 ◽  
Vol 9 (2) ◽  
pp. 90-93
Author(s):  
Zhuo Wang ◽  
Changwen Jing ◽  
Haixia Cao ◽  
SiWen Liu ◽  
Jianzhong Wu ◽  
...  

Author(s):  
Weiyang Lou ◽  
Bisha Ding ◽  
Jiannan Wang ◽  
Yongfang Xu

Recently, growing studies have demonstrated that circular RNAs (circRNAs) function as critical players in multiple human tumors, including papillary thyroid carcinoma (PTC). However, the expression and underlying potential mechanism of circRNAs in PTC are still not fully elucidated. In this study, 14 candidate differentially expressed circRNAs (DECs) between normal thyroid tissues and benign thyroid tissues or PTC were first screened using the GSE93522 dataset by the GEO2R online tool. Then, the structural loop graphs of these 14 circRNAs were obtained through the CSCD database. After performing miRNA co-prediction by combination of CSCD and CRI databases, a potential circRNA-miRNA sub-network, consisting of 9 circRNAs and 21 miRNAs, was successfully constructed. Subsequently, the expression and prognostic values of these miRNAs were further determined by starBase, and two miRNAs, namely, miR-605-5p and miR-876-3p, were identified as key miRNAs in PTC. Then, their downstream target genes were predicted by the miRNet database. CTNNB1 and CCND1 were found to be two most potential targets of miR-876-3p by combination of multiple in silico analyses, including protein–protein interaction (PPI), hub gene screening, correlation analysis, and expression analysis. Conclusively, we established a key hsa_circ_0088494-miR-876-3p-CTNNB1/CCND1 axis linked to carcinogenesis and progression of PTC, which may provide promising therapeutic targets in treating PTC in the future.


2013 ◽  
Vol 29 (4) ◽  
pp. 1415-1420 ◽  
Author(s):  
XIN LIU ◽  
MENGZI HE ◽  
YUFEI HOU ◽  
BING LIANG ◽  
LONGYU ZHAO ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Yali Yin ◽  
Shubin Hong ◽  
Shuang Yu ◽  
Yanrui Huang ◽  
Shuwei Chen ◽  
...  

Background. MicroRNA (miRNA) dysregulation was commonly seen in papillary thyroid carcinoma (PTC), andmiR-195was verified to be downregulated in PTC by the large data set analysis from The Cancer Genome Atlas (TCGA). Our study aimed to explore the biological functions and the underlying molecular mechanisms ofmiR-195in PTC.Methods. The relative expression ofmiR-195and its target genes were assessed by quantitative RT-PCR assay in 38 pairs of PTC and the adjacent thyroid tissues. Assays were performed to evaluate the effect ofmiR-195on the proliferation, migration, and invasion in PTC cell lines. Moreover, we searched for targets ofmiR-195and explored the possible molecular pathway ofmiR-195in PTC.Results. We found thatmiR-195was downregulated in PTC cell lines and tissues. Overexpression ofmiR-195significantly inhibited cell proliferation, migration, and invasion in K1 and BCPAP cell lines.CCND1andFGF2, which had inverse correlations withmiR-195in clinical specimens, were found to be the direct targets ofmiR-195. Furthermore,miR-195might be involved in PTC tumorigenesis by suppressing the Wnt/β-catenin signaling pathway.Conclusions. These results highlight an important role ofmiR-195in the initiation and progression of PTC and implicate the potential application ofmiR-195in PTC target therapy.


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