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 Long non-coding RNA LINC00704 promotes cell proliferation, migration, and invasion in papillary thyroid carcinoma via miR-204-5p/HMGB1 axis

2020 ◽  
Vol 15 (1) ◽  
pp. 561-571
Author(s):  
Yihui Lin ◽  
Jianjia Jiang
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Migration And Invasion ◽  
Papillary Thyroid ◽  
Cell Migration And Invasion ◽  
Non Coding Rna ◽  
Long Non Coding Rna

AbstractPapillary thyroid carcinoma (PTC) is a common malignancy worldwide. LncRNA LINC00704 (mitotically associated long non-coding RNA) was reported as a crucial regulator in PTC. However, the biological mechanism of LINC00704 action remains unclear in PTC. The mRNA levels of LINC00704, miR-204-5p, and high-mobility group box 1 (HMGB1) were measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay. HMGB1, proliferating cell nuclear antigen (PCNA), and cyclin D1 protein levels were detected using the Western blot assay. The binding relationship between miR-204-5p and LINC00704 or HMGB1 was predicted by LncBase Predicted v.2 or TargetScan, respectively, and then validated by dual luciferase reporter assay. Cell viability, cell cycle, cell migration and invasion, and migration ratio were assessed by MTT, flow cytometry, transwell cell migration and invasion, and wound-healing assays, respectively. Results suggested that LINC00704 and HMGB1 were elevated and miR-204-5p decreased in PTC tissues and cells. Furthermore, rescue experiments demonstrated that the miR-204-5p inhibitor alleviated the inhibitory effects of LINC00704 knockdown on cell proliferation, cell cycle, migration, and invasion. Meanwhile, miR-204-5p overexpression repressed proliferation, migration, and invasion by targeting HMGB1. Mechanical analysis discovered that LINC00704 could act as an miR-204-5p sponge to modulate HMGB1 expression. In conclusion, LINC00704 promoted PTC cell proliferation, cell cycle, migration, and invasion by the miR-204-5p/HMGB1 axis, providing a novel therapeutic target for PTC patients.

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 The impact of CLAUDIN-1 on follicular thyroid carcinoma aggressiveness

2015 ◽  
Vol 22 (5) ◽  
pp. 819-830 ◽  
Author(s):  
Denise Zwanziger ◽  
Julia Badziong ◽  
Saskia Ting ◽  
Lars Christian Moeller ◽  
Kurt Werner Schmid ◽  
...  
Keyword(s):  
Cell Migration ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Follicular Thyroid Carcinoma ◽  
Regional Lymph Node ◽  
Migration And Invasion ◽  
Cell Nuclei ◽  
Membrane Expression ◽  
Cell Migration And Invasion ◽  
The Impact

CLAUDIN-1 belongs to the family of transmembrane tight junction proteins tightening the paracellular cleft of epithelial cells. In human malignancies, CLAUDIN-1 is often dysregulated and located in subcellular compartments, particularly in the nucleus where it may influence cellular behaviour. Here, we studied CLAUDIN-1 in relation to the biological characteristics of follicular thyroid carcinoma (FTC). CLAUDIN-1 immuno-staining showed loss of membrane expression and increased nuclear CLAUDIN-1 localization in FTC metastases. CLAUDIN-1 function was further investigated in two different follicular thyroid carcinoma cell lines: FTC-133 isolated from a regional lymph node metastasis and FTC-238 derived from a lung metastasis. In both cell lines CLAUDIN-1 expression was demonstrated in the cell nuclei with a significantly higher protein expression in FTC-238 compared to FTC-133 cells. Interestingly, in vitro scratch assay revealed enriched nuclear CLAUDIN-1 expression near the scratch. Furthermore, the increase of the pathogenic character of FTC-133 cells by RASV12 transfection was associated with elevated CLAUDIN-1 expression and enhanced cell migration, invasion and proliferation. Likewise over-expression of nuclear CLAUDIN-1 in FTC-133 cells resulted in increased cell migration and invasion. Conversely, CLAUDIN-1 downregulation in FTC-238 cells by siRNA resulted in decreased cell migration and invasion and was accompanied by reduced phosphoPKC expression. Moreover, activation and inhibition of PKC resulted in CLAUDIN-1 up- and downregulation in FTC cells respectively. These data suggest an impact of CLAUDIN-1 on follicular thyroid carcinoma aggressiveness, which could potentially be influenced by PKC activity.

scholarly journals IL13RA2 Is Differentially Regulated in Papillary Thyroid Carcinoma vs Follicular Thyroid Carcinoma

2019 ◽  
Vol 104 (11) ◽  
pp. 5573-5584 ◽  
Author(s):  
Siao Ting Chong ◽  
Khee Ming Tan ◽  
Catherine Y L Kok ◽  
Shou Ping Guan ◽  
Siang Hui Lai ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Thyroid Cancer ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Papillary Thyroid ◽  
Thyroid Carcinomas ◽  
Advanced Tumor

Abstract Context The interleukin-13 receptor alpha2 (IL13RA2), which is known to be overexpressed in glioblastoma multiforme, plays a role in various cellular processes such as cell migration that may contribute to tumor progression. Studies have attributed IL13RA2 to invasion and metastasis in cancers of the ovary, breast, and pancreas, but the pathological role of IL13RA2 in thyroid cancer is still unclear. Objective This study aims to evaluate IL13RA2 expression in thyroid carcinomas and to examine the role of IL13RA2 in the progression of papillary thyroid carcinoma (PTC). Methods IL13RA2 immunochemical staining was performed on tissue microarrays of 137 thyroid carcinomas from patients, and the differential profile of IL13RA2 was validated in thyroid cancer cell lines. In PTC cell lines, we functionally assessed the effects of IL13RA2 underexpression and overexpression on cell proliferation, cell migration, and epithelial-mesenchymal transition (EMT) by using CCK-8, transwell migration assay, quantitative RT-PCR, and Western blot analysis. Results IL13RA2 expression was significantly correlated with advanced tumor T stage (pT3 or pT4; P = 0.001) and regional lymph node metastasis (pN1; P < 0.001). The staining scores of IL13RA2 were significantly higher in PTC compared with follicular subtypes (P < 0.001) and correlated with advanced tumor stage among PTC samples (pT3 or pT4; P = 0.028). Knockdown of IL13RA2 in B-CPAP cells significantly reduced cell viability, cell migration, and EMT markers including N-cadherin, Vimentin, and Snail. Exogenous overexpression of IL13RA2 in K1 cells increased cell migration and EMT, although cell proliferation was not affected. Conclusion IL13RA2 is differentially regulated in PTC and is involved in cell migration by enhancing EMT.

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 Sevoflurane represses the migration and invasion of gastric cancer cells by regulating forkhead box protein 3

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110059
Author(s):  
Fangfang Yong ◽  
Hemei Wang ◽  
Chao Li ◽  
Huiqun Jia
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cell Lines ◽  
Migration And Invasion ◽  
Control Group ◽  
Gastric Cancer Cells ◽  
Cell Migration And Invasion ◽  
Forkhead Box ◽  
Induced Apoptosis

Objective Previous studies suggested that sevoflurane exerts anti-proliferative, anti-migratory, and anti-invasive effects on cancer cells. To determine the role of sevoflurane on gastric cancer (GC) progression, we evaluated its effects on the proliferation, migration, and invasion of SGC7901, AGS, and MGC803 GC cells. Methods GC cells were exposed to different concentrations of sevoflurane (1.7, 3.4, or 5.1% v/v). Cell viability, migration, and invasion were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assays. Immunohistochemical staining and immunoblotting were performed to analyze forkhead box protein 3 (FOXP3) protein expression in tissue specimens and cell lines, respectively. Results FOXP3 was downregulated in human GC specimens and cell lines. Functionally, FOXP3 overexpression significantly inhibited the proliferation, migration, and invasion of GC cells and accelerated their apoptosis. Moreover, sevoflurane significantly blocked GC cell migration and invasion compared with the findings in the control group. However, FOXP3 silencing neutralized sevoflurane-induced apoptosis and the inhibition of GC cell migration and invasion. Sevoflurane-induced apoptosis and the suppression of migration and invasion might be associated with FOXP3 overactivation in GC cells. Conclusions Sevoflurane activated FOXP3 and prevented GC progression via inhibiting cell migration and invasion in vitro.

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

scholarly journals Metabolomic Alterations in Thyrospheres and Adherent Parental Cells in Papillary Thyroid Carcinoma Cell Lines: A Pilot Study

2018 ◽  
Vol 19 (10) ◽  
pp. 2948 ◽  
Author(s):  
Paola Caria ◽  
Laura Tronci ◽  
Tinuccia Dettori ◽  
Federica Murgia ◽  
Maria Santoru ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Krebs Cycle ◽  
Metabolic Phenotype ◽  
Gas Chromatography Mass Spectrometry ◽  
Papillary Thyroid ◽  
Time Data ◽  
Krebs Cycle Intermediates ◽  
New Biomarkers

Papillary thyroid carcinoma (PTC), is characterized by a heterogeneous group of cells, including cancer stem cells (CSCs), crucially involved in tumor initiation, progression and recurrence. CSCs appear to have a distinct metabolic phenotype, compared to non-stem cancer cells. How they adapt their metabolism to the cancer process is still unclear, and no data are yet available for PTC. We recently isolated thyrospheres, containing cancer stem-like cells, from B-CPAP and TPC-1 cell lines derived from PTC of the BRAF-like expression profile class, and stem-like cells from Nthy-ori3-1 normal thyreocyte-derived cell line. In the present study, gas chromatography/mass spectrometry metabolomic profiles of cancer thyrospheres were compared to cancer parental adherent cells and to non cancer thyrospheres profiles. A statistically significant decrease of glycolytic pathway metabolites and variations in Krebs cycle metabolites was found in thyrospheres versus parental cells. Moreover, cancer stem-like cells showed statistically significant differences in Krebs cycle intermediates, amino acids, cholesterol, and fatty acids content, compared to non-cancer stem-like cells. For the first time, data are reported on the metabolic profile of PTC cancer stem-like cells and confirm that changes in metabolic pathways can be explored as new biomarkers and targets for therapy in this tumor.

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