scholarly journals The Involvement of the hsa_circ_0088494-miR-876-3p-CTNNB1/CCND1 Axis in Carcinogenesis and Progression of Papillary Thyroid Carcinoma

2020 ◽  
Vol 8 ◽  
Author(s):  
Weiyang Lou ◽  
Bisha Ding ◽  
Jiannan Wang ◽  
Yongfang Xu
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Target Genes ◽  
Circular Rnas ◽  
Papillary Thyroid ◽  
Online Tool ◽  
Hub Gene ◽  
Protein Protein Interaction ◽  
Downstream Target ◽  
Structural Loop

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.

scholarly journals CircLDLR Promotes Papillary Thyroid Carcinoma Tumorigenicity by Regulating miR-637/LMO4 Axis

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yuan-ming Jiang ◽  
Wei Liu ◽  
Ling Jiang ◽  
Hongbin Chang
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Papillary Thyroid ◽  
Induced Apoptosis

Background. Circular RNAs (circRNAs) have been reported to play important roles in the development and progression of papillary thyroid carcinoma (PTC). However, the function and molecular mechanism of circRNA low-density lipoprotein receptor (circLDLR) in the tumorigenesis of PTC remain unknown. Results. In this study, circLDLR was found to be markedly upregulated in PTC tissues and cell lines, and knockdown of circLDLR inhibited PTC cell proliferation, migration, and invasion but induced apoptosis in vitro. Moreover, circLDLR acted as a sponge for miR-637, and miR-637 interference reversed the anticancer effects of circLDLR knockdown on PTC cells. LMO4 was verified to be a target of miR-637; LMO4 upregulation abolished miR-637 mediated inhibition of cell growth and metastasis in PTC. Additionally, circLDLR could indirectly modulate LMO4 via acting as a sponge of miR-637 in PTC cells. Besides that, xenograft analysis showed that circLDLR knockdown suppressed tumor growth in vivo via regulating LMO4 and miR-637. Conclusion. Taken together, these results demonstrated that circLDLR promoted PTC tumorigenesis through miR-637/LMO4 axis, which may provide a novel insight into the understanding of PTC tumorigenesis and be useful in developing potential targets for PTC treatment.

scholarly journals LncRNA GAS8-AS1 suppresses papillary thyroid carcinoma cell growth through the miR-135b-5p/CCND2 axis

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
NingHeng Chen ◽  
DeTao Yin ◽  
Bing Lun ◽  
XueLi Guo
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Cell Growth ◽  
Thyroid Carcinoma ◽  
Cell Cycle Progression ◽  
Gene Prediction ◽  
Tumor Formation ◽  
Cell Counting ◽  
Papillary Thyroid ◽  
Downstream Target

AbstractThe aim of the present study was to investigate the potential role of GAS8 antisense RNA 1 (GAS8-AS1) in papillary thyroid carcinoma (PTC). PcDNA3.1-GAS8-AS1 and si-GAS8-AS1, miR-135b-5p mimic and si-CCND2 were transfected into PTC cells. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8). QRT-PCR was used to determine expressions of GAS8-AS1, miR-135b-5p, and CCND2, and Western blot were detected protein level of CCND2. The miRNA target gene prediction site TargetScan was used to predict potential targets of GAS8-AS1 and miR-135b-5p. Cell cycle progression was analyzed by flow cytometry. We found that GAS8-AS1 was down-regulated in PTC cell lines and inhibited proliferation and cycle of PTC cell. GAS8-AS1 directly targets miR-135b-5p, and GAS8-AS1 could regulate a downstream target of miR-135b-5p, Cyclin G2 (CCNG2), in an miR-135b-5p-mediated manner. In addition, we also proved that overexpressed GAS8-AS1 inhibited tumor formation in vivo. GAS8-AS1 suppresses PTC cell growth through the miR-135b-5p/CCND2 axis.

scholarly journals Microarray profiling of circular RNAs in human papillary thyroid carcinoma

PLoS ONE ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. e0170287 ◽  
Author(s):  
Nianchun Peng ◽  
Lixin Shi ◽  
Qiao Zhang ◽  
Ying Hu ◽  
Nanpeng Wang ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Circular Rnas ◽  
Papillary Thyroid ◽  
Microarray Profiling

scholarly journals Profile and clinical implication of circular RNAs in human papillary thyroid carcinoma

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5363 ◽  
Author(s):  
Huihui Ren ◽  
Zhelong Liu ◽  
Siyue Liu ◽  
Xinrong Zhou ◽  
Hong Wang ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Expression Profile ◽  
Critical Role ◽  
Expression Level ◽  
Biological Behavior ◽  
Receiver Operating Curve ◽  
Circular Rnas ◽  
Papillary Thyroid ◽  
Qrt Pcr

Background Differently expressed circular RNAs (circRNAs) have been reported to play a considerable role in tumor behavior; however, the expression profile and biological function of circRNAs in papillary thyroid carcinoma (PTC) remains unknown. Thus, the study was aimed to characterize the circRNA expression profile to comprehensively understand the biological behavior of PTC. Methods We investigated the expression profile of circRNAs using circRNA microarray in three pairs of PTC and adjacent normal tissues. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to validate eight candidate circRNAs in 40 paired PTC tumors and adjacent normal samples. Next, we employed a bioinformatics tool to identify putative miRNA and circRNA-associated downstream genes, followed by constructing a network map of circRNA-miRNA-mRNA interactions and exploring the potential role of the candidate circRNAs. Results In total, 206 up- and 177 downregulated circRNAs were identified in PTC tissues (fold change >1.5; P < 0.05). The expression levels of eight candidate circRNAs confirmed by qRT-PCR were significantly different between the PTC and normal samples. The downstream genes of candidate circRNAs participated in various biological processes and signaling pathways. The most up and downregulated circRNAs were hsa_circRNA_007148 and hsa_circRNA_047771. The lower expression level of hsa_circRNA_047771 was associated BRAFV600 mutation, lymph node metastasis (LNM), as well as with advanced TNM stage (all P < 0.05). The higher expression level of hsa_circRNA_007148 was significantly correlated with LNM (P < 0.05). The areas under receiver operating curve were 0.876 (95% CI [0.78–0.94]) for hsa_circRNA_047771 and 0.846 (95% CI [0.75–0.96]) for hsa_circRNA_007148. Discussion The study suggests that dysregulated circRNAs play a critical role in PTC pathogenesis. PTC-related hsa_circRNA_047771 and hsa_circRNA_007148 may serve as potential diagnostic biomarkers and prognostic predictors for PTC patients.

scholarly journals Circ_LDLR promoted the development of papillary thyroid carcinoma via regulating miR-195-5p/LIPH axis

2020 ◽  
Author(s):  
Xiaolong Gui ◽  
Yan Li ◽  
Xiaobin Zhang ◽  
Ka Su ◽  
Wenlong Cao
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Colony Formation ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Papillary Thyroid ◽  
Cell Colony

Abstract Background: Emerging studies have demonstrated that circular RNAs (circRNAs) are key regulators for tumorigenesis in cancers, including papillary thyroid carcinoma (PTC). In this study, we aimed to explore the effects of circ_LDLR on PTC. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the levels of circ_LDLR, miR-195-5p and lipase H (LIPH). RNase R digestion assay and Actinomycin D assay were utilized to analyze the characteristics of circ_LDLR. Colony formation assay and 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay were conducted to evaluate cell proliferation. Western blot assay was used for the determination of protein levels. Flow cytometry analysis was applied to determine cell apoptosis. Transwell assay was performed to determine cell migration and invasion. Dual-luciferase reporter assay was used to verify the associations among circ_LDLR, miR-195-5p and LIPH. The murine xenograft model was constructed to explore the roles of circ_LDLR in vivo. Results: Compared to normal tissues and cells, circ_LDLR was upregulated in PTC tissues and cells. Silencing of circ_LDLR suppressed PTC cell colony formation, proliferation, migration and invasion and promoted apoptosis in vitro and hampered tumor growth in vivo. For mechanism investigation, circ_LDLR could regulate LIPH expression via sponging miR-195-5p. Moreover, miR-195-5p inhibition restored the effects of circ_LDLR knockdown on the malignant behaviors of PTC cells. MiR-195-5p overexpression inhibited PTC cell colony formation, proliferation, migration and invasion and facilitated apoptosis by targeting LIPH. Conclusion: Circ_LDLR knockdown decelerated PTC progression by regulating miR-195-5p/LIPH axis, which might provide a novel therapeutic target for PTC.

scholarly journals Novel DNMT3A Germline Variant in a Patient with Multiple Paragangliomas and Papillary Thyroid Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3304
Author(s):  
Sara Mellid ◽  
Javier Coloma ◽  
Bruna Calsina ◽  
María Monteagudo ◽  
Juan M. Roldán-Romero ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Target Genes ◽  
Papillary Thyroid ◽  
Pwwp Domain ◽  
Gain Of Function ◽  
Dna Profile ◽  
Whole Exome ◽  
Bilateral Carotid

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.

scholarly journals Down-regulated HSDL2 expression suppresses cell proliferation and promotes apoptosis in papillary thyroid carcinoma

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Jing Zeng ◽  
Xiao Ma ◽  
Jinjing Wang ◽  
Ran Liu ◽  
Yun Shao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Target Genes ◽  
Mrna Level ◽  
Papillary Thyroid ◽  
Bioinformatics Analyses ◽  
In Vivo Experiments

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.

Sign in / Sign up

Export Citation Format

Share Document