Migration Of Thyroid Cancer Cells Research Articles

Canagliflozin reduces thyroid cancer cells migration in vitro by inhibiting CXCL8 and CCL2: An additional anti-tumor effect of the drug

PurposeCanagliflozin exert anti-cancer effects in several types of cancer including thyroid cancer (TC). However, whether it could modulate chemokines secreted in TC microenvironment is still unknown. The aim of the present study is to evaluate whether Canagliflozin could inhibit pro-tumorigenic chemokines CXCL8 and CCL2 and/or the TC cell migration induced by them. Experimental designTC cell lines, TPC-1 and 8505C, HUVEC and normal thyroid cells NHT were treated with increasing concentrations of Canagliflozin. Viability was assessed by WST-1 and colony formation/proliferation by cristal violet. Chemokines were measured in cell supernatants by ELISA. mRNAs were evaluated by RT-PCR. TC migration (trans-well) and HUVEC proliferation (cristal violet) were assessed by treating cells with Canagliflozin alone or in combination with CXCL8 or CCL2. ResultsCanagliflozin reduced TC, HUVEC and NHT cells viability. The ability to form colonies of TC and the HUVEC proliferation (basal and CXCL8 or CCL2-induced) was also inhibited. mRNA and the secretion of CXCL8 was reduced in all cell types. The secretion of CCL2 was reduced by Canagliflozin in all cell types whereas its mRNA levels were reduced only in TPC-1. IL-6 was reduced in all cell types, while CXCL10 increased. More interestingly the CXCL8 and CCL2-induced TC cell migration as well as HUVEC proliferation was inhibited by Canagliflozin in both cell types. ConclusionCanagliflozin exerts anti-cancer effects not only by reducing TC viability or colonies formation, but also by modulating two pro-tumorigenic chemokines resulting in reduced TC cells migration. These results expand the spectrum of canagliflozin-promoted anti-cancer effects.

Abstract C012: Exploring thrombospondin-1 variant and splicing factors as potential diagnostic biomarkers and therapeutic targets in thyroid cancer

Abstract Thyroid cancer is the most common type of cancer affecting the thyroid gland, accounting for 11.8% of all cancer cases in Korea as of 2020. The majority of thyroid cancer cases belong to the papillary thyroid cancer (PTC) subtype. Diagnostic methods for thyroid cancer include blood tests, ultrasound examinations, fine needle aspiration cytology (FNAC), PET/CT scans, and others. However, distinguishing between different subtypes of thyroid cancer, such as follicular variant of papillary thyroid carcinoma (FVPTC), follicular adenoma (FA), and follicular thyroid carcinoma (FTC), remains challenging, often leading to unnecessary surgeries for patients. In this study, antibody arrays were used to analyze tumor and adjacent normal tissues from thyroid cancer patients. Thrombospondin 1 (TSP1), was found to be more highly expressed in tumor tissue compared to normal tissue. TSP1 is a glycoprotein with diverse biological functions that can either inhibit or promote tumorigenesis depending on the context. The researchers discovered a transcriptional variant of TSP1 (TSP1V) generated by intron retention (IR), which was more highly expressed in normal tissue compared to tumor tissue. Overexpression of TSP1V in thyroid cancer cells resulted in the secretion of the protein into the medium or its deposition in the extracellular matrix (ECM). TSP1V exhibited anti-cancer properties, inhibiting proliferation, migration, invasion, colony formation, and spheroid formation of thyroid cancer cells in vitro. It also suppressed tumor growth in a mouse experiment. The researchers explored the TGF-β pathway, a well-known signaling pathway associated with TSP1, and found that TSP1V inhibited the phosphorylation of Smad2 and FAK, unlike TSP1 wild-type (TSP1W). To investigate the mechanism behind TSP1V's generation through IR, we examined splicing factors. RBM5 overexpression inhibited IR induced by anti-cancer compounds, while RBM5 knockdown increased IR. Sulindac sulfide, one of the compounds tested, increased IR by inhibiting the phosphorylation of RBM5. Additionally, trans-chalcone was found to increase IR by demethylating DNA. Trans-chalcone also reduced the expression of TSP1W, DNMT3b, and MeCP2 in a time-dependent manner. The study concluded by analyzing tumor and adjacent normal tissues from patients with follicular neoplasm (FN), including benign thyroid nodule (BTN) and differentiated thyroid carcinoma (DTC). We also observed significant differences in the ratio of TSP1V to TSP1W. These findings provide evidence that secreted proteins like TSP1 have the potential to serve as diagnostic biomarkers and therapeutic targets for thyroid cancer. Moreover, the study enhances our understanding of the molecular mechanisms underlying the anti-cancer activities of these proteins. Citation Format: Yukyung Hong, Ilju Kim, Hyunjin Moon, Jaehak Lee, Pattawika Lertpatipanpong, Chang Hwan Ryu, Junsun Ryu, Seung Joon Baek. Exploring thrombospondin-1 variant and splicing factors as potential diagnostic biomarkers and therapeutic targets in thyroid cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C012.

Acute exposure to diesel particulate matter promotes collective cell migration in thyroid cancer cells

Several ecological studies suggest that ambient air pollution is associated with the occurrence of thyroid cancer. In this study, we used certified diesel particulate matter as a proxy for fine particulate matter. Human thyroid cancer cell lines 8505C and TPC-1 were incubated with different concentrations of NIST1650b for 5 days and subjected to functional assays. We found that NIST1650b treatment did not affect short-term cell growth but reduced colony formation at high concentrations. Notably, NIST1650b-treated cells showed altered morphology toward cluster coalescence following treatment. Wound healing assays revealed that leading-edge cells formed protruding tips while maintaining cell-cell adhesion, and a significantly higher ratio of wound closure following treatment at 10 μg/mL was seen in both cell lines. A weak stimulatory effect on transwell cell migration was observed in 8505C cells. Taken together, our results suggest that fine particulate matter induced a coherent phenotype accompanied by augmented collective cell migration in thyroid cancer cells.

Construction and validation of a PANoptosis-related lncRNA signature for predicting prognosis and targeted drug response in thyroid cancer.

Thyroid cancer (TC) is the most prevalent malignancy of the endocrine system. PANoptosis, a newly discovered cell death pathway, is of interest in tumor research. However, the relationship between PANoptosis-related lncRNAs (PRlncRNAs) and TC remains unclear. The study aimed to develop a prognostic model based on PRlncRNAs in TC. Gene expression data of PANoptosis-associated genes and clinical information on TC from The Cancer Genome Atlas (TCGA) database were analyzed by Pearson correlation analysis, univariate/multivariate Cox analysis, and Lasso Cox regression analysis. A PRlncRNA signature was constructed and used to develop a nomogram to predict overall survival (OS). We further explored the correlation between the risk score and tumor immune microenvironment, immune checkpoints, and drug sensitivity. Moreover, we verified the expression and biological function of lncRNAs in TC cell lines. Finally, seven PRlncRNAs were used to construct a prognostic model for predicting the OS of TC patients. We found that the risk score was associated with the tumor microenvironment (TME) and the expression of critical immune checkpoints. In addition, we screened for drugs that high- or low-risk TC groups might be sensitive to. Quantitative real-time polymerase chain reaction (qRT-PCR) results showed differential expression of four PRlncRNAs (GAPLINC, IDI2-AS1, LINC02154, and RBPMS-AS1) between tumor and normal tissues. Besides, a GEO database (GSE33630) was used to verify the expression differences of PRLncRNAs in THCA tissues and normal tissues. Finally, RBPMS-AS1 was found to inhibit the proliferation and migration of TC cells. In conclusion, we developed a PANoptosis-related lncRNA prognostic risk model that offers a comprehensive understanding of TME status in patients with TC and establishes a foundation for the choice of sensitive medications and immunotherapy.

Knockdown of long non-coding RNA SNHG3 inhibits proliferation, migration and invasion of human thyroid cancer via miR-339-5p/GPR62 axis

Previous studies have implicated SNHG3, a long non-coding RNA, in various human cancers, suggesting its oncogenic role. However, its specific involvement in thyroid cancer and the underlying molecular mechanisms remain unclear. Therefore, this study aims to elucidate the role of SNHG3 in human thyroid cancer and its interaction with the miR-339-5p/GPR62 axis. Understanding these mechanisms could provide insights into potential therapeutic targets for managing thyroid cancer. Results revealed significant upregulation of SNHG3 in human thyroid cancer tissues and cell lines. Knockdown of SNHG3 significantly suppressed proliferation, migration and invasion of CUTC5 and IHH-4 thyroid cancer cells. Knockdown of SNHG3 induces apoptosis in CUTC5 and IHH-4 cells and also inhibits the growth of xenografted tumors in vivo. Different in vitro assays revealed the interaction of SNHG3 with microRNA-339-5p (miR-339-5p) in thyroid cancer cells. Expression of miR-339-5p was significantly downregulated in thyroid cancer tissues and cell lines. However, the knockdown of SNHG3 caused significant upregulation of miR-339-5p. Interestingly, overexpression of miR-339-5p exerted tumor-suppressive effects in CUTC5 and IHH-4 cells via post-transcriptional suppression of GPR62. Knockdown of GPR62 significantly inhibited the proliferation, migration and invasion of CUTC5 and IHH-4 cells. Nonetheless, inhibition of miR-339-5p or overexpression of GPR62 avoids the growth inhibitory effects of SNHG3 knockdown in CUTC5 and IHH-4 cells. Results indicated that SNHG3 exerts oncogenic molecular function in thyroid cancer via miR-339-5p/GPR62 axis and may act as a therapeutic target for its management.

Proliferation and migration of ML1 follicular thyroid cancer cells are inhibited by IU1 targeting USP14: role of proteasome and autophagy flux.

USP14 is a deubiquitinating enzyme involved in protein degradation by interacting with the proteasome and removal of poly-ubiquitin chains on target proteins. USP14 can influence cellular processes such as cell survival, DNA repair, ER stress, endocytosis, and the inflammatory response. USP14 further plays a role in tumor growth, and the inhibition of USP14 by compounds such as IU1 may affect cancer cell migration and invasion. Here we have studied the mechanisms for the action of IU1 in ML1 follicular thyroid cancer cells, comparing them with control, primary thyroid cells. Treatment with IU1 reduced proliferation of ML1 cells in a concentration-dependent manner, and more prominently than in control cells. IU1 decreased basal migration of ML1 cells, and after stimulation of cells with the bioactive compound, sphingosine-1-phosphate. The sphingosine-1-phosphate receptor 3 was increased in ML1 cells as compared with control thyroid cells, but this was not influenced by IU1. Further studies on the mechanism, revealed that IU1 enhanced the proteasome activity as well as LC3B-dependent autophagy flux in ML1 cells with an opposite effect on control thyroid cells. This indicates that IU1 elicits a cell-type dependent autophagy response, increasing it in ML1 cancer cells. The IU1-mediated stimulation of autophagy and proteasomes can likely contribute to the reduced cell proliferation and migration observed in ML1 cells. The precise set of proteins affected by IU1 in ML1 thyroid and other cancer cells warrant further investigations.

MEX3A induces the development of thyroid cancer via targeting CREB1.

Thyroid cancer is a prevalent form of endocrine cancer, and its global incidence has been steadily increasing. MEX3A is a protein that is known to be highly expressed in various human malignant tumors, including thyroid cancer, and it has been linked to patient prognosis. However, the molecular mechanisms underlying MEX3A's tumorigenic capabilities in thyroid cancer are not fully understood. In this study, we aimed to investigate the role of MEX3A in thyroid cancer. We confirmed that MEX3A was overexpressed in both thyroid cancer tissues and cell lines. Additionally, we found a positive correlation between high levels of MEX3A and the AJCC stage. To further understand the functional significance of MEX3A in thyroid cancer, we depleted MEX3A expression in B-CPAP and TPC-1 cells. Interestingly, we observed a significant reduction in thyroid cancer cell proliferation and migration, as well as ameliorated cell apoptosis and arrested tumor growth upon MEX3A depletion. These findings strongly suggested that MEX3A played a critical role in the development of thyroid cancer. Furthermore, our study uncovered an important interaction between MEX3A and CREB1 (cAMP response element-binding protein 1). The interaction between MEX3A and CREB1 appeared to contribute to the tumor-promoting effects of MEX3A in thyroid cancer by directly targeting CREB1. Silencing CREB1 was observed to alleviate the malignant phenotypes promoted by MEX3A in thyroid cancer cells. Together, this study highlighted the importance of the MEX3A-CREB1 interaction in thyroid cancer development and suggested the therapeutic potential of targeting MEX3A for the treatment of this disease.

Jagged 1 Regulates The Proliferation and Metastasis of Human MDA-T68 Thyroid Cancer Cells.

The current study evaluated the expression profile and explored the therapeutic implications of Jagged 1 in human thyroid cancer. This experimental study was conducted in 60 paired specimens of papillary thyroid and adjacent normal tissues. Gene expression was determined by quantitative real time polymerase chain reaction (qRT-PCR) and western blotting. Transfection of cancer cells was performed by using Lipofectamine 2000. The cell proliferation of PTC cells was estimated by MTT assay. Clonogenic assay was performed for analysis of colony forming potential of cancer cells. The apoptosis of PTC cells was studied by using AO/EB and Annexin V-FITC/PI staining methods. Flow cytometry was done to analyze the cell cycle phase distribution of cancer cells. Migration and invasion PTC cells were determined respectively with the wound-healing and transwell assays. The impact of Jagged 1 silencing was investigated in vivo in a xenografted mice model followed by Immunohistochemistry (IHC) analysis. We found significant (P<0.05) upregulation of Jagged 1 in human thyroid cancer. Silencing of Jagged 1 caused significant (P<0.05) reduction in proliferation and colony formation of MDA-T68 cells. The inhibitory effects of Jagged 1 silencing were found to be due to the induction of apoptosis. We also found enhancement of Bax and repression of Bcl-2 protein levels in MDA-T68 cells. Wound healing assay indicated significant (P<0.05) inhibition of cell migration of MDA-T68 thyroid cancer cells. Additionally, we found that invasion of the thyroid cancer cells was reduced by 55% upon silencing of Jagged 1. Moreover, Jagged 1 silencing was found to cause inhibition of the Notch intracellular domain (NICD) and Notch target gene, Hes-1 expression. Finally, Jagged 1 silencing inhibited the xenografted tumors in vivo. The findings suggest that Jagged 1 regulates the development of thyroid cancer that may act as a therapeutic target for managing thyroid cancer.

PLS3 promotes papillary thyroid carcinoma progression by activating the Notch signaling pathway.

Thyroid cancer is the most common endocrine malignancy worldwide. Although significant progress has been made in understanding the genetic and molecular alterations that drive thyroid cancer, the mechanisms underlying thyroid tumor progression remain unclear. In this study, we explored the involvement of Plastin-3 (PLS3) in the progression of papillary thyroid cancer and elucidated the underlying molecular mechanisms. We first analyzed clinical samples from papillary thyroid cancer patients and found that PLS3 expression was significantly upregulated in tumor tissues compared to adjacent normal tissues. Moreover, high PLS3 expression was associated with advanced tumor stage and poor prognosis. Further in vitro and in vivo experiments showed that PLS3 could promote the proliferation, migration, and invasive behavior of papillary thyroid cancer cells, while PLS3 knockdown suppressed these processes. Mechanistically, we found that PLS3 promoted papillary thyroid cancer progression by activating the Notch signaling pathway. Specifically, PLS3 upregulated the expression of Notch receptors (Notch1) and downstream target gene (Hes1) in papillary thyroid cancer cells. In summary, our findings collectively indicate that PLS3 plays a pivotal role in driving the progression of papillary thyroid cancer and holds promise as a viable therapeutic target for the treatment of this disease.

PLA2R1 Inhibits Differentiated Thyroid Cancer Proliferation and Migration via the FN1-Mediated ITGB1/FAK Axis.

PLA2R1 is a novel gene that is aberrantly expressed in a variety of malignancies. However, the role and mechanism of PLA2R1 in thyroid cancer has not been elucidated. We aimed to uncover the underlying mechanism of PLA2R1 in thyroid cancer. We collected 115 clinical specimens, including 54 tumor tissues and 61 para-cancerous tissues, who underwent surgical treatment at Shanghai Tenth Hospital. Immunohistochemical staining was used to evaluate PLA2R1 expression in differentiated thyroid cancer (DTC) tissues. The thyroid cancer cell lines 8505c and FTC133 transfected with PLA2R1 overexpression or knockdown plasmids were used for CCK8 assays and a wound healing assay. Next, we conducted coimmunoprecipitation (Co-IP) experiments and western blotting to explore the underlying mechanism of PLA2R1 in regulating the growth of thyroid cancer. We discovered that the expression of PLA2R1 was lower in the tumor tissues than in para-cancerous tissues (χ2 = 37.0, p < 0.01). The overexpression of PLA2R1 significantly suppressed thyroid cancer cell proliferation and migration, and both of these effects were partially attenuated by the knockdown of PLA2R1. Furthermore, the in vivo growth of DTC could be alleviated by the knockdown of PLA2R1. The mechanistic study revealed that PLA2R1 competed with FN1 for binding to ITGB1, inhibiting the FAK axis and epithelial-mesenchymal transition (EMT). We speculate that PLA2R1 might be a promising marker and a novel therapeutic target for thyroid cancer.

The Role of MMP-9 and MMP-9 Inhibition in Different Types of Thyroid Carcinoma.

Matrix metalloproteinase-9 (MMP-9), one of the most investigated and studied biomarkers of the MMPs family, is a zinc-dependent proteolytic metalloenzyme whose primary function is degrading the extracellular matrix (ECM). It has been proved that MMP-9 expression elevates in multiple pathological conditions, including thyroid carcinoma. MMP-9 has a detectable higher level in malignant or metastatic thyroid tumor tissues than in normal or benign tissues and acts as an additional marker to distinguish different tumor stages because of its close correlations with clinical features, such as lymph node metastasis, TNM stage, tumor size and so on. Natural and non-natural MMP-9 inhibitors suppress its expression, block the progression of diseases, and play a role in therapy consequently. MMP-9 inhibitory molecules also assist in treating thyroid tumors by suppressing the proliferation, invasion, migration, metastasis, viability, adhesion, motility, epithelial-mesenchymal transition (EMT), and other risk factors of different thyroid cancer cells. In a word, discovering and designing MMP-9 inhibitors provide great therapeutic effects and promising clinical values in various types of thyroid carcinoma.

Abstract 3616: Investigating proto-oncogene PBF-induced cell migration and invasion

Abstract The proto-oncogene pituitary tumor transforming gene binding factor (PTTG1IP/PBF) is overexpressed in multiple tumors and associated with tumor progression. PBF mediates several tumorigenic processes, including cell motility, whereby it potently induces cancer cell migration and invasion. PBF is phosphorylated by Src kinase at Y174 and mutation of this residue (Y174A) renders PBF unable to induce cell invasion, suggesting that phosphorylation mediates the stimulation of cancer cell motility by PBF. This study aimed to further elucidate the mechanism of PBF-induced cell motility. PBF-Y174 is also the key residue in a YXXΦ endocytosis motif. Both PBF phosphorylation and endocytosis were found to be essential for PBF-induced cell motility as mutants which disrupted either process were unable to stimulate thyroid and breast cancer cell migration and invasion. To elucidate molecular events downstream of PBF overexpression, phosphoproteomic and RNA-Seq analyses of normal thyroid cells (Nthy-ori 3-1) with stable PBF overexpression were performed and showed an enrichment in molecules involved in cell adhesion and cytoskeleton organisation. These findings prompted further investigation into a physiological role for PBF in cell motility. We utilised a novel Pbf knockout (Pbf−/−) mouse model generated through CRISPR/Cas9-mediated deletion of Pbf exon 4 in C57BL/6N mice to determine the impact of Pbf deletion on cellular mechanisms. Mouse embryonic fibroblasts (MEFs) were isolated at embryonic day 13.5 and used as primary cultures. Pbf−/- MEFs showed a significant reduction in migration and invasion compared with wild-type (Pbf+/+) MEFs. Interestingly, the loss of one functional copy of Pbf in heterozygote MEFs (Pbf+/−) resulted in an intermediate decrease in motility suggesting a gene-dosage effect. Initial immunofluorescent studies of Pbf−/− MEFs suggest alterations in focal adhesions (FAs). In Pbf+/+ MEFs focal adhesion kinase (FAK) and paxillin staining highlighted FA structures that were normally elongated and aligned with actin stress fibers. In contrast, Pbf−/- MEFs demonstrated a significant reduction in FAK and paxillin staining with smaller, punctate and more radially distributed FAs. These studies demonstrate a physiological role for PBF in cell adhesion and migration and further elucidate the mechanism by which PBF induces cell motility in tumor progression. Citation Format: Merve Kocbiyik, Selvambigai Manivannan, Ling Zha, Katie Brookes, Martin L Read, Chris J McCabe, Vicki E Smith. Investigating proto-oncogene PBF-induced cell migration and invasion. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3616.

Identification of m6A-associated LncRNAs as predict factors for the immune infiltration and prognosis of thyroid cancer

Objective This study aims to evaluate the prognostic value of m6A-associated long noncoding RNAs (lncRNAs) and their interaction with tumour microenvironment in thyroid cancer (THCA). Methods The clinical and gene expression data of tumours from 502 patients with THCA and 58 adjacent normal tissues were retrieved from The Cancer Genome Atlas (TCGA)–THCA dataset. The Pearson test was utilized to identify potential m6A-associated lncRNAs (p < 0.001 and Pearson correlation coefficient > 0.4). Quantitative real-time polymerase chain reaction was performed to verify the expression levels of lncRNAs in tissues. MTT, EdU, colony formation and wound-healing assays were performed to determine the functions of m6A-associated lncRNAs in THCA cell proliferation and metastasis. Results M6A-associated lncRNAs were identified in three cluster groups. A significant survival difference was found among them, with cluster 1 patients showing worse survival. Moreover, lower immune and estimate scores were correlated to poorer prognosis, and CD8+ T cell and memory CD4+ T cell levels were increased in cluster 1. Cluster 2, with better overall survival, had high expression of PD-L1 and CTLA-4. Eleven of the m6A-associated lncRNAs were screened to establish the risk model, including AC007365.1, AC008555.1, AC040160.1, AC064807.1, AC126773.4, AL023583.1, AL512306.2, EIF2AK3-DT, LINC00667, LYPLAL1-DT and MIR181A2HG. Based on the median risk score, THCA patients were stratified into low-risk and high-risk groups. Overall survival analysis showed a dramatic difference between the two groups. qRCR was performed to verify the expression levels of lncRNA (LYPLAL1-DT, EIF2AK3-DT and MIR181A2HG) in THCA and adjacent normal tissues. Furthermore, functional experiments showed that knockdown of MIR181A2HG obviously inhibited the proliferation and migration of papillary thyroid cancer (PTC) cells in vitro, whereas LYPLAL1-DT overexpression promoted PTC cell proliferation and migration. Conclusions Eleven of the m6A-associated lncRNAs were identified as a risk model to predict clinical outcomes and provide a novel and efficient immunotherapeutic strategy for THCA patients. Key messages m6A-associated lncRNAs can be used to predict the clinical outcomes of thyroid cancer patients. An m6A-associated lncRNAs risk model, which can accurately evaluate the immune status and risk stratification in individual thyroid cancer patients, was established. Knockdown/overexpression of representative lncRNAs in the risk model significantly affected the proliferation and migration of papillary thyroid cancer cells.

Intracellular FGF1 promotes invasion and migration in thyroid carcinoma via HMGA1 independent of FGF receptors.

Fibroblast growth factor 1 (FGF1) is extensively amplified in many tumors and accelerates tumor invasion and metastasis. However, the role and precise molecular mechanism by which FGF1 participates in thyroid cancer (TC) are still unclear. Quantitative real-time polymerase chain reaction- and western blotting were used to detect the mRNA and protein levels of FGF1, high mobility group A (HMGA1), epithelial-to-mesenchymal transition (EMT)-related factors, and FGFs in both TC tissues and cell lines. Immunohistochemistry was conducted to examine the expression of FGF1 and HMGA1. Immunofluorescence staining was used to detect the coexpression of FGF1 and HMGA1. Transwell and wound healing assays were conducted to evaluate the effects of FGF1 on the capacity of invasion and migration in cells. FGF1 was upregulated in papillary thyroid carcinoma (PTC) tissues and cell lines and was relatively higher in PTC tissues with cervical lymph node metastasis. Furthermore, FGF1 promotes invasion and metastasis through the EMT pathway. Mechanistically, FGF1 promotes EMT through intracellular function independent of FGF receptors. Interestingly, we demonstrated that FGF1 could upregulate HMGA1 in TC cells, and the correlation of FGF1 and HMGA1 was positive in PTC tissues. FGF1 and HMGA1 had obvious colocalization in the nucleus. We further revealed that FGF1 promotes the invasion and migration of TC cells through the upregulation of HMGA1. Intracellular FGF1 could promote invasion and migration in TC by mediating the expression of HMGA1 independent of FGF receptors, and FGF1 may be an effective therapeutic target in TC.

TBK1 promotes thyroid cancer progress by activating the PI3K/Akt/mTOR signaling pathway.

Thyroid cancer has received increasing attention; however, its detailed pathogenesis and pathological processes remain unclear. We investigated the role of TANK-binding kinase 1 (TBK1) in the progression of thyroid cancer. The expression of TBK1 in thyroid cancer and normal control tissues was analyzed using real-time quantitative polymerase chain reaction. The function of TBK1 on thyroid cancer cells was detected using MTT, colony formation, wound healing, and Transwell assays. The xenograft assay was carried out to check on the role of TBK1 in thyroid cancer. TBK1 was highly expressed in thyroid tumors. High expression of TBK1 raised viability, proliferation, migration, and invasion of thyroid cancer cells. Gene set enrichment analysis revealed that TBK1 activated the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin pathway. In addition, Myc-associated zinc finger protein (MAZ) was overexpressed in thyroid cancer and transcriptionally activated BK1. MAZ silence reversed the effects of TBK1 overexpression on thyroid cancer progression. Cotransfection with MAZ small-interfering RNA(siRNA) and TBK1 siRNA did not strengthen the inhibitory effect of TBK1 silencing on the thyroid cancer cells. The xenograft tumor assay showed that TBK1 short hairpinRNA inhibited tumor growth. MAZ silencing inhibited tumor progress of thyroid cancer cells, whereas this inhibitory effect was reversed by TBK1 overexpression.

Ellagic acid inhibits cell proliferation, migration, and invasion of anaplastic thyroid cancer cells via the Wnt/β-catenin and PI3K/Akt pathways.

Anaplastic thyroid cancer (ATC) is a rare but lethal human malignant cancer with no known cure. Ellagic acid (EA), a natural plant extract, has shown antitumor activity against multiple cancers; however, its effects on the malignant phenotypes of ATC cells remain unknown. This study aimed to evaluate the effects of EA on proliferation, migration, and invasion of ATC cells and further explore the associated signaling mechanisms. The normal human thyroid cell line Nthy-ori3-1 and ATC cell line BHT-101 were used. Cytotoxicity assay was performed using the Cell Counting kit-8 (CCK-8) assay. Cell proliferation, migration, and invasion assays were performed using the CCK-8 and colony formation, wound healing, and Transwell invasion assays, respectively. Western blotting was used to detect the levels of related proteins. β-catenin nuclear protein levels were measured to evaluate the Wnt/β-catenin pathway. The phosphorylation level of the Akt protein was measured and calculated to evaluate the PI3K/Akt pathway. LiCl and IGF-1 were used as pathway agonists to determine the involvement of the corresponding pathway. The results showed that EA inhibited the proliferation, migration, and invasion of ATC cells. Furthermore, both the Wnt/β-catenin and PI3K/Akt pathways were suppressed by EA treatment, and activation of these two pathways reversed the EA-induced inhibition of the pathological phenotypes of ATC cells. These findings demonstrate that EA inhibits proliferation, migration, and invasion of ATC cells by suppressing the Wnt/β-catenin and PI3K/Akt pathways, suggesting that EA is a potential drug candidate for treating ATC and provides a theoretical basis for further in vivo experiments and clinical applications.

Retraction.

Retraction: "Downregulated long noncoding RNA LINC00313 inhibits the epithelial-mesenchymal transition, invasion, and migration of thyroid cancer cells through inhibiting the methylation of ALX4," by Xingzhi Zhao and Xinhua Hu, J Cell Physiol. 2019; 20992-21004: The above article, published online on 15 May 2019 in Wiley Online Library (https://doi.org/10.1002/jcp.28703), has been retracted by agreement between the authors, the journal's Editor-in-Chief, Prof Dr Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed after the authors stated that unintentional errors occurred during the research process, and the experimental results cannot be verified. The investigation, based on allegation by a third party revealed duplications and an image element of the experimental data published elsewhere in a different scientific context. As a consequence, the consider conclusions of this article are considered invalid.

S100A6 promotes the development of thyroid cancer and inhibits apoptosis of thyroid cancer cells through the PI3K/AKT/mTOR pathway

High levels of S100A6 have been associated with progression in some types of human cancers. Cancers related to S100A6 have been reported to include lung cancer, cervical cancer, pancreatic cancer, gastric cancer, colon cancer, etc., but its role in the molecular pathogenesis of these cancers is largely unknown. This study investigated the expression and functional roles of S100A6 in human thyroid cancer. The expression level of S100A6 in thyroid cancer cells was determined by bioinformatics and transcriptomic analysis. Furthermore, the potential functions of S100A6 in tumorigenesis were analyzed by cell proliferation, migration, invasion, and Western blot assays in human thyroid cancer cells. Public database queries revealed high S100A6 expression in thyroid cancer. In addition, we also found that high expression of S100A6 was positively correlated with malignant clinicopathological characteristics of thyroid cancer in The Cancer Genome Atlas database. qPCR results confirmed the high expression of S100A6 in thyroid cancer cells. S100A6 silencing inhibited cell proliferation, migration, and invasion. Western blot assays and response experiments showed that S100A6 promotes cell proliferation and tumorigenicity partly through the PI3K/AKT/mTOR signaling pathway. These results suggest that S100A6 affects the progression of thyroid cancer and can be used as a target in the future treatment of thyroid cancer.

Circ_0124055 promotes the progression of thyroid cancer cells through the miR-486-3p/MTA1 axis.

Thyroid cancer is one of the malignancy cancers. CircRNA, a non-coding RNA, plays an important role in the development of cancer. The relationship and roles of circ_0124055, miR-486-3p and MTA1 in thyroid cancer have not been reported. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to analyze the RNA levels of circ_0124055, miR-486-3p and MTA1. Western blot was conducted to analyze the protein levels of MTA1, Epithelial cadherin (E-cadherin) and Neuro cadherin (N-cadherin). Subcellular localization assay was used to analyze circ_0124055 location in thyroid cancer cells. Colony formation assay and 5-Ethynyl-2'-deoxyuridine (EdU) assay were carried out to analyze cell proliferation. Cell migration and invasion were analyzed by wound-healing assay and transwell assay. Flow cytometry assay was performed to investigate cell apoptosis. Dual-luciferase reporter assay and RIP assay were employed to analyze the interactions among circ_0124055, miR-486-3p and MTA1. Immunohistochemical (IHC) assay was performed to assess the expression of Ki67, MTA1 and E-cadherin in tumor tissues. Thyroid cancer tumor growth in vivo was evaluated by tumor xenograft mouse model assay. The expression of circ_0124055 was up-regulated in tumor tissues and cells. Knockdown of circ_0124055 could inhibit thyroid cancer cell proliferation, migration and invasion and promote cell apoptosis, accompanied by the dysregulation of E-cadherin and N-cadherin expression. Circ_0124055 could target miR-486-3p, and miR-486-3p could target MTA1. MiR-486-3p inhibitor could restore the effect of circ_0124055 knockdown in the progression of thyroid cancer. Moreover, MTA1 overexpression weakened the inhibitory effects of miR-486-3p mimics on the progression of thyroid cancer. Further, circ_0124055 could influence tumor growth in vivo. Circ_0124055 promoted the progression of thyroid cancer cells through the miR-486-3p /MTA1 axis.

Retracted: CCL18 Knockdown Suppresses Cell Growth and Migration in Thyroid Cancer.

[This retracts the article DOI: 10.1155/2022/1548155.].