scholarly journals MiR-195Inhibits Tumor Growth and Metastasis in Papillary Thyroid Carcinoma Cell Lines by TargetingCCND1andFGF2

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Yali Yin ◽  
Shubin Hong ◽  
Shuang Yu ◽  
Yanrui Huang ◽  
Shuwei Chen ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Target Therapy ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Papillary Thyroid ◽  
Data Set

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.

scholarly journals Gold Nanoparticles Suppressed Proliferation, Migration, and Invasion in Papillary Thyroid Carcinoma Cells via Downregulation of CCT3

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Fangzhou Liu ◽  
Dawei Ma ◽  
Wei Chen ◽  
Xinyuan Chen ◽  
Yichun Qian ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Molecular Mechanisms ◽  
Target Therapy ◽  
Migration And Invasion ◽  
Control Group ◽  
Papillary Thyroid ◽  
And Migration ◽  
Induced Apoptosis

Emerging evidences have demonstrated that gold nanoparticles (AuNPs) have been used for cancer treatment. The aim of this study was to investigate the effects and molecular mechanisms of AuNPs on papillary thyroid carcinoma (PTC) cells (BCPAP and TPC-1). Characterizations of AuNPs were detected by UV-Vis spectra, transmission electron microscopy (TEM), and dynamic light scattering (DLS). Cell proliferation and apoptosis, migration, and invasion of PTC cells were evaluated by MTT, flow cytometry, wound healing, and transwell assays, respectively. Furthermore, qRT-PCR and western blot assays were performed to assess the protein expressions related to apoptosis and migration including caspase-3, caspase-9, Bax, Bcl-2, MMP-2, and MMP-9. The study revealed that AuNPs significantly suppressed cell viability, migration, and invasion and remarkably induced apoptosis of BCPAP and TPC-1 cells compared with the control group. Moreover, AuNPs negatively regulated the expression of CCT3 and silencing of CCT3 obviously promoted the proliferation, migration, and invasion inhibition and apoptosis induction of PTC cells combined with AuNPs. Collectively, these results highlighted the potential application of AuNPs in PTC target therapy.

scholarly journals MiR-192-5p inhibits proliferation, migration, and invasion in papillary thyroid carcinoma cells by regulation of SH3RF3

2021 ◽  
Vol 41 (9) ◽  
Author(s):  
Songbo Fu ◽  
Chengxu Ma ◽  
Xulei Tang ◽  
Xiaoni Ma ◽  
Gaojing Jing ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Mrna Level ◽  
Ring Finger ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Pcr Analysis ◽  
Papillary Thyroid ◽  
Anti Cancer

Abstract Background: The decreased level of miR-192-5p has been reported in several kinds of cancers, including bladder, colon, ovarian, and non-small cell lung cancer. However, the expression and function of miR-192-5p in papillary thyroid carcinoma/cancer (PTC) remains unknown. Objective: The present study aimed to explore the function and underlying mechanism of miR-192-5p in PTC development. Methods: PTC tissues and relative normal controls from PTC patients were collected. qRT-PCR analysis was performed to measure miR-192-5p and SH3RF3 mRNA level in PTC tissues and cell lines. CCK-8 method and FCM assay were used to test cell proliferation and apoptosis in TPC-1 cells, respectively. The abilities of cell migration and invasion were detected by wound healing and transwell assays, respectively. The protein expression was evaluated by Western blot. The interaction between miR-192-5p and Src homology 3 (SH3) domain containing ring finger 3 (SH3RF3) were confirmed by dual-luciferase reporter assay. Results: MiR-192-5p level was obviously decreased in PTC tissues and cell lines. Overexpression of miR-192-5p suppressed proliferation, migration, invasion, and EMT process, while induced apoptosis in TPC-1 cells. In addition, miR-192-5p negatively modulated SH3RF3 expression by binding to its 3′-untranslated region (3′UTR). Silencing SH3RF3 inhibited the migration, invasion, and EMT of TPC-1 cells. In the meantime, matrine, an alkaloid extracted from herb, exerted its anti-cancer effects in PTC cells dependent on increase in miR-192-5p expression and decrease in SH3RF3 expression. Conclusion: We firstly declared that miR-192-5p played a tumor suppressive role in PTC via targeting SH3RF3. Moreover, matrine exerted its anti-cancer effects in PTC via regulating miR-192-5p/SH3RF3 pathway.

scholarly journals Depletion of VAX2 restrains the malignant progression of papillary thyroid carcinoma by modulating ERK signaling pathway

2019 ◽  
Vol 14 (1) ◽  
pp. 237-245
Author(s):  
Bei Guo ◽  
Yi Zhang ◽  
Kun Yuan ◽  
Feng-Xia Jiang ◽  
Qian-Bo Cui ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Western Blot ◽  
Signaling Pathway ◽  
Malignant Progression ◽  
The Cancer Genome Atlas ◽  
Cell Counting ◽  
Erk Signaling ◽  
Migration And Invasion ◽  
Papillary Thyroid

AbstractObjectiveVentral anterior homeobox 2 (VAX2) gene is a key regulating factor for the development of the ventral region of the eye, and has recently attracted much attention from the cancer treatment field. Our study aimed to explore the effect of VAX2 on papillary thyroid carcinoma (PTC).MethodsWe determined the expression levels of VAX2 in PTC based on The Cancer Genome Atlas (TCGA) database. We then assessed the prognosis of patients with PTC, and analyzed the association between VAX2 expression and clinicopathological characteristics. Subsequently, we measured the biological functions of VAX2 in PTC using qRT-PCR, cell counting kit-8 (CCK-8) assay, colony formation assay, wound healing assay, transwell assays and western blot.ResultsVAX2 was up-regulated in PTC tissues when compared with normal thyroid tissues, and high expression level of VAX2 was positively correlated with poor prognosis. Furthermore, knockdown of VAX2 significantly inhibited the proliferation, migration and invasion of PTC cells. Importantly, through western blot analysis, we found that the expression of phosphorylated-(p) ERK and p-MEK in ERK signaling pathway showed a significant decrease after knockdown of VAX2.ConclusionThese findings suggest that VAX2 may be involved in the malignant progression of PTC, and hold significant potential as a therapeutic target for PTC.

scholarly journals Identification of Potential lncRNAs and miRNAs as Diagnostic Biomarkers for Papillary Thyroid Carcinoma Based on Machine Learning

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Fei Yang ◽  
Jie Zhang ◽  
Baokun Li ◽  
Zhijun Zhao ◽  
Yan Liu ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Epigenetic Modifications ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Endothelial Cell Migration ◽  
Papillary Thyroid ◽  
Diagnostic Biomarkers

Background. Papillary thyroid carcinoma (PTC) accounts for most of the proportion of thyroid cancer (TC). The objective of this study was to identify diagnostic, differentially expressed long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), contributing to understanding the epigenetics mechanism of PTC. Methods. The data of lncRNA, miRNA, and mRNA were downloaded from the Cancer Genome Atlas (TCGA) dataset, followed by functional analysis of differentially expressed mRNAs. Optimal diagnostic lncRNA and miRNA biomarkers were identified via random forest. The regulatory network between optimal diagnostic lncRNA and mRNAs and optimal diagnostic miRNA and mRNAs was identified, followed by the construction of ceRNA network of lncRNA-mRNA-miRNA. Expression validation and diagnostic analysis of lncRNAs, miRNAs, and mRNAs were performed. Overexpression of ADD3-AS1 was performed in PTC-UC3 cell lines, and cell proliferation and invasion assay were used for investigating the role of ADD3-AS1 in PTC. Results. A total of 107 differentially expressed lncRNAs, 81 differentially expressed miRNAs, and 515 differentially expressed mRNAs were identified. 11 lncRNAs and 6 miRNAs were regarded as the optimal diagnostic biomarkers for PTC. The epigenetic modifications via the above diagnostic lncRNAs and miRNAs were identified, including MIR181A2HG-FOXP2-hsa-miR-146b-3p, BLACAT1/ST7-AS1-RPS6KA5-hsa-miR-34a-5p, LBX2-AS1/MIR100HG-CDHR3-hsa-miR-34a-5p, ADD3-AS1-PTPRE-hsa-miR-9-5p, ADD3-AS1-TGFBR1-hsa-miR-214-3p, LINC00506-MMRN1-hsa-miR-4709-3p, and LOC339059-STK32A-hsa-miR-199b-5p. In the functional analysis, MMRN1 and TGFBR1 were involved in cell adhesion and endothelial cell migration, respectively. Overexpression of ADD3-AS1 inhibited cell growth and invasion in PTC cell lines. Conclusion. The identified lncRNAs/miRNAs/mRNA were differentially expressed between normal and cancerous tissues. In addition, identified altered lncRNAs and miRNAs may be potential diagnostic biomarkers for PTC. Additionally, epigenetic modifications via the above lncRNAs and miRNAs may be involved in tumorigenesis of PTC.

scholarly journals TET1 is a Tumor Suppressor That Inhibits Papillary Thyroid Carcinoma Cell Migration and Invasion

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Shuang Yu ◽  
Yali Yin ◽  
Shubin Hong ◽  
Siting Cao ◽  
Yanrui Huang ◽  
...  
Keyword(s):  
Cell Migration ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Mrna Expression ◽  
Cell Lines ◽  
Migration And Invasion ◽  
Epithelial Cell Line ◽  
Papillary Thyroid ◽  
Cell Migration And Invasion ◽  
5Hmc Level

Background. Ten-eleven translocation (TET) enzymes catalyze the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) promoting demethylation in cells. However, the expression pattern and biologic significance of TET in papillary thyroid carcinoma (PTC) remain unclear. This study aimed to elucidate the biological functions of TET1 and the miRNA and mRNA expression levels in PTC cells with downregulated TET1. Methods. The expression of the TET family in 49 PTC tissues and corresponding tumor-adjacent tissues, as well as PTC cell lines (BCPAP, K1, and TPC-1) and the normal thyroid epithelial cell line (Nthy-ori 3-1), were detected using quantitative real-time polymerase chain reaction. The 5hmC level was detected in PTC tissues and cell lines using immunohistochemistry and dot blot assay, respectively. After silencing the TET1 gene with siRNAs in BCPAP and TPC-1 cells, cell proliferation was detected using EdU assay. Transwell assay was used to investigate cell migration and invasion. miRNA and mRNA expression arrays were conducted in TET1-depleted BCPAP cells. Results. The expression level of TET1 decreased in PTC tissues and cell lines and was consistent with the reduction in the 5hmC level. The knockdown of the TET1 gene promoted cell migration and invasion in BCPAP cells. The expression of miR-7, miR-15/16 cluster, and let-7 family was downregulated, while the expression of let-7e was upregulated after siRNA-TET1 treatment in BCPAP cells. The expression of WNT4, FZD4, CDK6, MCF2L, and EDN1 was upregulated as potential target genes of dysregulated miRNAs. Conclusion. The study showed that TET1 dysfunction inhibited the migration and invasion of BCPAP cells and might have a potential role in the pathogenesis of PTC.

scholarly journals lncRNA-miRNA-mRNA ceRNA Network in Thyroid Carcinoma from The Cancer Genome Atlas

2020 ◽  
Author(s):  
Guoheng Mo ◽  
Qunguang Jiang ◽  
Zixuan Wang ◽  
Zhaoting Zheng ◽  
XiaoSi Chen
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Molecular Mechanisms ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Papillary Thyroid ◽  
Cerna Network ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Abstract Increasing evidence indicates that the competitive endogenous RNA (ceRNA) hypothesis, that is, long non-coding RNA (LncRNA) can competitively bind microRNA (miRNA) through miRNA response elements to affect the expression of target RNA, and dysregulation of LncRNA expression plays a key role in tumor progression. The papillary thyroid carcinoma that we studied is the most significant pathological type of thyroid cancer, but its ceRNA network has not been extensively evaluated. We analyzed level-3 data from RNA-Seq of 58 para-carcinoma tissues and 501 patients with primary papillary thyroid carcinoma (PTC) using the DEseq software package and downloaded clinical information from The Cancer Genome Atlas (TCGA) to find potential biomarkers or therapeutic targets. As a result, 149 differential miRNAs were selected, including 117 up -regulated, 32 down-regulated, and 3099 differential mRNAs, including 1976 up-regulated, 1123 down-regulated, and 434 differential lncRNAs, including 331 up-regulated and 103 down-regulated (Fold Change > 2, P < 0.05). The interactions between these differentially expressed RNA groups constitute the ceRNA network of PTC. Moreover, we used the microde database to predict the miRNAs that may be acted by the above screened differential lncRNAs and intersected with the selected miRNAs, and further predicted the target genes of the intersecting miRNAs by TargetScan, miRTarBase and miRDB, and intersected with the selected mRNAs. From the constructed ceRNA network we can see that Linc00460 may cause the invasion and metastasis of PTC by competitively inhibiting hsa-mir-150 and upregulating the expression of its downstream target gene EREG. Our study identified a series of lncRNAs associated with PTC progression and prognosis, and this complex ceRNA interaction network provides guidance for better understanding of the molecular mechanisms of PTC and can be used as an effective diagnostic tool for PTC invasion, metastasis and prognosis. Kaplan-Meier analysis of the differentially expressed RNAs associated with PTC pathogenesis confirmed that the lncRNAs AC097717.1, C20orf203, EMX2OS were potentially associated with the prognosis of PTC (P<0.05).

Identification of Differentially Expressed Genes Associated with Papillary Thyroid Carcinoma

2020 ◽  
Vol 23 (6) ◽  
pp. 546-553
Author(s):  
Hongyuan Cui ◽  
Mingwei Zhu ◽  
Junhua Zhang ◽  
Wenqin Li ◽  
Lihui Zou ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Mrna Level ◽  
Thyroid Tissue ◽  
Differentially Expressed ◽  
Thyroid Tumors ◽  
Papillary Thyroid

Objective: Next-generation sequencing (NGS) was performed to identify genes that were differentially expressed between normal thyroid tissue and papillary thyroid carcinoma (PTC). Materials & Methods: Six candidate genes were selected and further confirmed with quantitative real-time polymerase chain reaction (qRT-PCR), and immunohistochemistry in samples from 24 fresh thyroid tumors and adjacent normal tissues. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was used to investigate signal transduction pathways of the differentially expressed genes. Results: In total, 1690 genes were differentially expressed between samples from patients with PTC and the adjacent normal tissue. Among these, SFRP4, ZNF90, and DCN were the top three upregulated genes, whereas KIRREL3, TRIM36, and GABBR2 were downregulated with the smallest p values. Several pathways were associated with the differentially expressed genes and involved in cellular proliferation, cell migration, and endocrine system tumor progression, which may contribute to the pathogenesis of PTC. Upregulation of SFRP4, ZNF90, and DCN at the mRNA level was further validated with RT-PCR, and DCN expression was further confirmed with immunostaining of PTC samples. Conclusion: These results provide new insights into the molecular mechanisms of PTC. Identification of differentially expressed genes should not only improve the tumor signature for thyroid tumors as a diagnostic biomarker but also reveal potential targets for thyroid tumor treatment.

scholarly journals SUN-132 KLF5 Is a Poor Prognostic Marker and Therapeutic Target for Middle Eastern Papillary Thyroid Carcinoma

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Khawla S Al-Kuraya ◽  
Abdul K Siraj ◽  
Pratheeshkumar Poyil ◽  
Divya Padmaja ◽  
Sandeep Kumar Parvathareddy ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Therapeutic Target ◽  
Critical Role ◽  
Dependent Manner ◽  
Papillary Thyroid ◽  
Inhibition Of Proliferation ◽  
Over Expression

Abstract Thyroid cancer is the second most common malignancy among females in Saudi Arabia, with Papillary thyroid carcinoma (PTC) accounting for 80-90%. The Kruppel-like factor 5 (Klf5) is a transcription factor that play a critical role in cell transformation, proliferation and oncogenesis. Immunohistochemical analysis of KLF5 was performed in 1219 PTC cases. KLF5 over-expression was noted in 65.1% (793/1219) of PTCs, and was significantly associated with tall-cell variant (p &lt;0.0001), extrathyroidal extension (p = 0.0003), lymph node metastasis (p &lt; 0.0001) and stage IV tumors (p &lt; 0.0001). Significant association was also noted with HIF-1α over-expression (p = 0.0492). Interestingly, KLF5 over-expressing tumors showed poor disease-free survival (p = 0.0066). Functional studies in PTC cell lines showed that KLF5 co-immunoprecipitated with HIF-1α. Knockdown of KLF5 decreased the expression of HIF-1α while KLF5 was not affected by HIF-1α inhibition, suggesting that KLF5 is a functional upstream of HIF-1α. Down-regulation of KLF5 using specific inhibitor, ML264 or siRNA inhibited cell invasion and migration. In addition, treatment of PTC cell lines with ML264 resulted in inhibition of proliferation and induction of apoptosis in a dose-dependent manner. Furthermore, silencing of KLF5 significantly decreased the self-renewal ability of spheroids generated from PTC cells. Our findings confer that KLF5 may be a potential therapeutic target for the treatment of papillary thyroid cancer.

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 Differential glycolytic profile and Warburg effect in papillary thyroid carcinoma cell lines

2016 ◽  
Vol 36 (6) ◽  
pp. 3673-3681 ◽  
Author(s):  
Raquel Guimarães Coelho ◽  
Juliana De Menezes Cazarin ◽  
João Paulo Albuquerque Cavalcanti De Albuquerque ◽  
Bruno Moulin De Andrade ◽  
Denise P. Carvalho
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Warburg Effect ◽  
Carcinoma Cell ◽  
Papillary Thyroid ◽  
Carcinoma Cell Lines ◽  
Thyroid Carcinoma Cell ◽  
Papillary Thyroid Carcinoma Cell
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