Thyroid Cancer Cell Proliferation Research Articles

ZNF169 promotes thyroid cancer progression via upregulating FBXW10

BackgroundZinc finger protein 169 (ZNF169) plays a key role in cancer development. However, the specific role of ZNF169 in the tumorigenesis of thyroid carcinoma (THCA) remains poorly understood.MethodsThe expression of ZNF169 was measured using immunohistochemistry, RT-qPCR, and western blot. Cell proliferation was detected using CCK-8 assay and cell colony formation assays, while cell migration was determined by Transwell assay. Flow cytometry was used to detect cell apoptosis and cell cycle distribution. The interaction of ZNF169 and its downstream gene was studied using luciferase assay and CHIP-PCR. Recovery assay in cells and animals were also performed to demonstrate the mechanism.ResultsZNF169 was highly expressed in THCA tissues and cells lines compared with matched adjacent non-cancerous thyroid tissues or normal thyroid epithelial cell. Moreover, thyroid cancer cell proliferation and migration were suppressed following ZNF169 knockdown, while were potentiated by ZNF169 overexpression. ZNF169 also regulate THCA cell apoptosis and cell cycle progression. Mechanically, ZNF169 enhanced the transcription activity and expression of F-box/WD repeat-containing protein 10 (FBXW10) via the binding to its promoter. There was a positive correlation between ZNF169 and FBXW10 in THCA patients. In addition, knockdown of FBXW10 suppressed the proliferation of THCA cells. Recovery assays in vitro and in vivo demonstrated that FBXW10 knockdown reversed the effects of ZNF169 overexpression on THCA cell proliferation and tumor growth.ConclusionsIn summary, ZNF169 promotes THCA progression via upregulation of FBXW10, which may provide a novel theoretical basis for the development of clinical therapies for THCA.

Anti-cancer effect of midazolam via downregulating YWHAH in papillary thyroid cancer cells

The work is aimed to investigate whether midazolam functions in thyroid cancer and reveal the potential mechanism of action. Cell viability was detected by CCK-8 method when treated by varying doses of midazolam to detect the cytotoxicity of midazolam on human thyroid follicular epithelial cell line and thyroid cancer cell lines. In thyroid cancer cells, EDU staining, wound healing and transwell assays were respectively used to detect cell proliferation, migration and invasion. Western blot was used to detect the expressions of matrix metalloproteinases (MMPs). Flow cytometry assay, western blot and immunofluorescence staining were used to detect cell apoptosis. CB-Dock2 server predicted midazolam-tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH) interaction and western blot was also used to detect YWHAH expression. Midazolam dose-dependently decreased the viability of thyroid cancer cells and demonstrated no cytotoxicity on Nthy-ori-3-1 cells. In addition, increasing concentrations of midazolam or silencing of YWHAH significantly inhibited thyroid cancer cell proliferation, migration and invasion and induced cell apoptosis. Midazolam had a molecular binding with YWHAH and midazolam downregulated YWHAH expression. YWHAH partially reversed the impacts of midazolam on the cellular events in thyroid cancer. Collectively, midazolam may act as an anti-thyroid cancer agent via its interrelation with YWHAH.

Investigation of the Anticarcinogenic Effects of Hypericum perforatum Extract on Human Thyroid Cancer.

Plants and their bioactive compounds play a crucial role in the pharmaceutical industry for treating cancer. To date, the cytotoxic and antiproliferative effects of Hypericum perforatum methanol extract on human thyroid cancer cell lines have not been thoroughly explored. The present study aimed to assess the potential anti-cancer effects of HPME on human thyroid cancer and investigate its potential therapeutic benefits. HPME was prepared using the maceration method, and its antioxidant activity was examined. Cytotoxicity studies were then carried out, followed by an investigation of the possible effects of HPME on metastasis and colony-forming capacities of human thyroid cancer cells. Afterward, qRT-PCR, western blotting, and apoptosis assays were performed. Cytotoxicity studies revealed notable cytotoxicity of HPME against the TT cell line. Moreover, HPME significantly curtailed metastasis and invasion of TT cells in an in vitro wound healing assay. Analyses of gene expressions demonstrated an elevation in caspase-12, caspase-3, and Bax, coupled with a reduction in BcL-2, APOE, and CLU expression. Following HPME treatment, there was an increase in the protein expression levels of Bax and Caspase-12, while a decrease in the BcL-2, APOE, and CLU protein expression. Furthermore, apoptotic studies indicated an increase in early apoptosis. Overall results revealed that HPME demonstrates a notable antioxidant capacity in human thyroid cancer. It exerts an influence on crucial biological processes associated with cancer, indicating its potential to hinder the proliferation of human thyroid cancer cells by enhancing apoptosis through the upregulation of gene and protein expression, particularly involving caspases.

SOX13 as a potential prognostic biomarker linked to immune infiltration and ferroptosis inhibits the proliferation, migration, and metastasis of thyroid cancer cells.

SOX13 is a transcription factor belonging to the SOX family. SOX proteins are critical regulators of multiple cancer progression, and some are known to control carcinogenesis. Nevertheless, the functional and clinical significance of SOX13 in human thyroid cancer (THCA) remain largely unelucidated. Data on SOX13 expression were obtained through The Cancer Genome Atlas together with Gene Expression Omnibus. Co-expression, differential expression, and functional analyses of genes were investigated by databases. Associations between SOX13 levels, immune infiltration, ferroptosis, and immune checkpoint gene levels were analyzed. Genetic changes in SOX13 were investigated using CBioPortal. Associations between SOX13 levels and THCA clinicopathological features were analyzed and nomogram modeling for diagnostic and prognostic prediction. The influence of SOX13 on proliferation, migration, and metastasis was determined in KTC-1 and TPC-1 cell lines. SOX13 was significantly lower in THCA tumors compared to controls. In addition, upregulated SOX13 gene mutation were evident in thyroid cancer. SOX13-associated genes exhibited differential expression in pathways associated with thyroid cancer development. Significant associations were found between SOX13 levels, immune infiltration, ferroptosis, and immune checkpoint genes in THCA tissue. SOX13 levels correlated with THCA stage, histologic grade, and primary neoplasm focus types, and independently predicted overall and progression-free intervals. SOX13 expression effectively distinguished between tumor and normal thyroid tissue. Spearman correlations highlighted a significant relationship between SOX13 and ferroptosis-associated genes. Overexpression of SOX13 enhances the inhibition of RSL3 (iron death activator) on the cell viability of TPC-1. Higher SOX13 levels in Thyroid cancer cells may lead to reduced proliferation, migration, and metastasis by regulating ferroptosis. Reduced SOX13 expression inversely impacts patient prognosis. In addition, SOX13 strongly regulates cancer immunity and Ferroptosis. Hence, SOX13 has great promise as a bioindicator for both thyroid cancer prognosis and immune cell invasion.

FBP1 over-expression suppresses HIF-1α in papillary thyroid cancer

Papillary thyroid carcinoma (PTC) is generally a slow-growing disease with a favorable 10-year survival rate. However, about 10% of PTC cases show significant aggressiveness, with tendencies for local invasion or distant metastasis, the mechanisms of which remain unclear. This study aims to identify predictive indicators and explore new potential targets for clinical treatment, highlighting the need for novel biomarkers and therapeutic targets. We analyzed FBP1 expression in PTC tissues. Cell proliferation, apoptosis, and invasion were evaluated with and without FBP1 overexpression in PTC cells to assess FBP1’s effects. We then investigated whether FBP1 reduces PTC cell tumorigenesis and metastasis by regulating HIF-1α expression. FBP1 expression was reduced in PTC samples and showed a negative correlation with T stage. In vitro experiments indicated that FBP1 acts as a hypoxia response inhibitor, regulating tumor cells. Additionally, FBP1 inhibited the proliferation, apoptosis, and invasion of thyroid cancer cells by modulating HIF-1α expression. Our results provide new insights into the role of FBP1 in PTC progression and indicate that targeting the FBP1-HIF-1α axis could be a promising therapeutic approach for this disease.

CALML6 as a potential diagnostic marker for thyroid cancer promotes thyroid cancer cell proliferation via modulating the immune microenvironment

PurposeCALML6 is an inflammation-related gene, and its expression may be associated with cancer. Here we evaluated the role of CALML6 expression in papillary thyroid carcinoma (PTC). MethodsWe utilized databases such as The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx) and UALCAN to evaluate the relationship between CALML6 expression and clinicopathological features in thyroid cancer. Immunohistochemical assays were used to observe CALML6 expression in thyroid cancer tissues. The role of CALML6 in PTC cells was investigated using RNA interference. ResultsWe found CALML6 expression was lower than normal and associated with extrathyroidal extension, lymph node metastasis, pathological T stage, tall cell PTC and the expressions of immune checkpoint genes CD274 and PDCD1LG2 in THCA. Additionally, Immunohistochemical staining showed that CALML6 expression was significantly upregulated in thyroid cancer tissues. RNAi analysis showed that CALML6 knockdown significantly reduced cell growth and blocked the cell cycle of PTC cells. Conclusions: Our results suggest that CALML6 may be a novel diagnostic marker for PTC that is closely associated with the invasive and tall cell subtypes, and it may be a potential target for immunotherapy.

Serum small extracellular vesicles-derived BST2 as a biomarker for papillary thyroid microcarcinoma promotes lymph node metastasis

Papillary thyroid microcarcinoma (PTMC), although frequently indolent, could be aggressive in a few patients, leading to lymph node metastasis (LNM) and worsened prognosis. To explore the role of protein profiling of small extracellular vesicles (sEVs) in the auxiliary diagnosis and risk stratification of PTMC, proteins in serum sEVs isolated from PTMC patients with (N = 10) and without (N = 10) LNM and benign thyroid nodule (BN) patients (N = 9) were profiled via a bioinformatics-integrated data-independent acquisition proteomic technique. The performance of candidate proteins as diagnostic and prognostic biomarkers in PTMC was assessed via receiver operating characteristic analysis. We found that serum sEVs from PTMC patients promoted the proliferation and migration of human papillary thyroid cancer (PTC) cells and tube formation in human lymphatic endothelial cells (HLECs). SEV proteins from PTMC patients with and without LNM have differential expression profiles, with bone marrow stromal cell antigen 2 (BST2) being best associated with PTMC progression. Through knockdown and overexpression, we proved that the high expression of sEV-derived BST2 was bound up with higher proliferation and migration ability of PTC cells as well as stronger lymphangiogenesis in HLECs. This study brought insight into the differential sEV-protein profile with or without LNM in PTMC. The serum sEV-BST2 may contribute to PTMC progression and LNM and may have diagnostic, prognostic, and therapeutic implications.

Feasibility study of lncRNA DHRS4-AS1 sponge miR-222-3p in the diagnosis of thyroid cancer.

Thyroid cancer is a commonly occurring malignant tumour within the endocrine system, the incidence of which has been increasing steadily in our country. It has been the focus and direction of research in recent decades to continuously explore the diagnostic markers and molecular mechanisms of thyroid cancer and provide new possibilities for the healing of patients. In this study, lncRNA DHRS4-AS1 was identified as the research target, and the regulatory function of abnormal expression of DHRS4-AS1 on thyroid cancer was discussed. Thyroid cancer (116) and non-cancer normal (82) tissue samples were collected in this paper, and the expression of DHRS4-AS1 and miR-222-3p in tissues and cells were evaluated by RT-qPCR. CCK-8 and flow cytometry were used to detect cell survival status. The mechanism of DHRS4-AS1 sponge miR-222-3p was analysed by dual-luciferase reporter gene detection. In the present study, DHRS4-AS1 was down-regulated in both thyroid tissue and cell samples, while miR-222-3p expression was elevated. The ROC curve reflected the diagnostic value of DHRS4-AS1 in thyroid cancer [area under the curve (AUC) = 0.887, sensitivity = 76.7%, specificity = 95.1%]. DHRS4-AS1 regulates the development of thyroid cancer by targeting miR-222-3p. In addition, in vitro experiments demonstrated that overexpression of DHRS4-AS1 (pcDNA3.1-DHRS4-AS1) inhibited the proliferation of thyroid cancer cells and promoted cell apoptosis, while down-regulating the level of miR-222-3p. DHRS4-AS1 acts as a miR-222-3p sponge in thyroid cancer, and overexpression of DHRS4 AS1 down-regulates cell proliferation and promotes cell apoptosis. These findings demonstrate the potential of DHRS4-AS1 as a diagnostic factor for thyroid cancer.

Human adipose-derived stem cells promote migration of papillary thyroid cancer cell via leptin pathway

Introduction Obesity is associated with the incidence and poor prognosis of thyroid cancer, but the mechanism is not fully understood. The aim of this study was to investigate the effects of human adipose-derived stem cells (ADSCs) on the invasion and migration of thyroid cancer cells. Methods ADSCs-conditioned medium (ADSC-CM) was collected to culture thyroid cancer cell lines TPC-1 cells and BCPAP cells. The effects of ADSCs on thyroid cancer cell proliferation were determined by CCK8 and EdU assays, and the effects on migration were determined by Transwell and wound closure assays. Leptin neutralizing antibodies (NAB) were added to ADSC-CM to block leptin. In animal experiments, TPC-1 cells and BCPAP cells were injected into the tail vein of nude mice, and the leptin receptor antagonist peptide allo-aca was injected subcutaneously to block the leptin pathway. The number and size of metastatic lung tumours were observed after 8 weeks. Results ADSC-CM significantly promoted the invasion and migration of thyroid cancer cells and upregulated their matrix metalloproteinase 2 (MMP-2) levels, while NAB with the addition of leptin reduced the invasion and migration of thyroid cancer cells and downregulated MMP-2 levels. Allo-aca treatment reduced the number of metastatic lung nodules formed by thyroid cancer cells in nude mice and reduced the diameter of metastatic lesions. Conclusion ADSCs upregulate MMP-2 levels of thyroid cancer cells through exocrine leptin, thereby promoting cancer cell migration, which may be one of the key mechanisms by which obesity increases the invasiveness of thyroid cancer.

Vitamin D receptor polymorphisms associate with the efficacy and toxicity of radioiodine-131 therapy in patients with differentiated thyroid cancer.

Radioiodine-131 (I-131) therapy is the common postoperative adjuvant therapy for differentiated thyroid cancer (DTC) However, methods to evaluate the efficacy and toxicity of I-131 on DTC are still lacking. To evaluate the association between vitamin D receptor (VDR) gene polymorphisms and the efficacy and toxicity of I-131 in DTC patients. A total of 256 DTC patients who received I-131 therapy were enrolled. The patients were divided into effective group and ineffective group. 4 single nucleotide polymorphisms (SNPs) (rs7975232, rs731236, rs1544410 and rs10735810) of VDR were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) Cell counting kit-8 (CCK-8) and flow cytometry were used to detect the proliferation and apoptosis of thyroid cancer cells. Patients in effective group had more CC genotype of rs7975232 and GG genotype of rs10735810 compared with patients in ineffective group They were also independent factors for influencing the efficacy of I-131. PTC-1 and FTC-133 cells transfected with CC genotype of rs7975232 showed lower proliferative activity and higher apoptosis rate after being treated with I-131 In addition, patients with CC genotype at rs7975232 had fewer adverse reactions after I-131 treatment. VDR gene polymorphisms may be associated with the efficacy and toxicity of I-131 in DTC patients, which will help to personalize the treatment for patients.

Investigating the mechanism of METTL16-dependent m6A modification regulating the SAMD11 protein signaling pathway to inhibit thyroid cancer phenotypes

Despite substantial progress in the research and treatment of thyroid cancer, many areas in the molecular mechanisms remain to be explored. This study aims to comprehensively and deeply investigate the key role and potential molecular mechanisms of RNA methyltransferase METTL16 in the development and progression of thyroid cancer. Firstly, through bioinformatics analysis of tumor databases, we examined the correlation between METTL16 expression levels and patient prognosis. Subsequently, immunofluorescence experiments on clinical patient tissue microarrays were conducted to validate these findings. We also compared the nucleic acid and protein expression levels of METTL16 in different cell lines. By integrating bioinformatics analysis of public databases, laboratory molecular biology experiments, and comprehensive data analysis, we revealed the high expression of METTL16 in clinical tissues and thyroid cancer cells, and confirmed its role in regulating the biological characteristics of cell proliferation, migration, and invasion in thyroid cancer through in vitro and in vivo experiments. Additionally, we identified SAMD11 as a target gene of METTL16 and further validated its importance and potential regulatory pathways in thyroid cancer.

Uncovering the connection between obesity and thyroid cancer: the therapeutic potential of adiponectin receptor agonist in the AdipoR2-ULK axis

Adiponectin, a unique adipose-derived factor, is significantly downregulated in obesity, making it a crucial target for tumor-related metabolic research. AdipoRon is a novel adiponectin receptor agonist with the advantages of a small molecular weight, high stability and a long half-life. By screening the cervical adipose tissue of papillary thyroid carcinoma (PTC) patients with adipokine antibody array, we found that adiponectin was a potential correlation factor between obesity and PTC progression. AdipoRon has oral activity and is easily absorbed and delivered to target tissues. The effects of AdipoRon on thyroid cancer have not been reported. In this study, we identified adiponectin receptor 1 (AdipoR1) and AdipoR2 on the surface of thyroid cancer cell lines. AdipoRon inhibited the proliferation and migration of thyroid cancer cells, limited energy metabolism in thyroid cancer cells, promoted differentiation of thyroid cancer cells, and induced autophagy and apoptosis. Mechanistic studies revealed that AdipoRon inhibited p-mTOR Ser2448 and p-p70S6K Thr389, and activated ULK1 and p-ULK1. ULK1 knockdown suppressed the effect of AdipoRon on LC3BII/I protein and lysosomes. AdipoR2 knockdown reduced AdipoRon-induced autophagy in thyroid cancer cells. This study is the first to demonstrate the role of AdipoRon in PTC. Our findings illustrate a previously unknown function and mechanism of the AdipoRon-AdipoR2-ULK/p-ULK1 axis in PTC and lay the foundation for clinical translation of AdipoRon to PTC. Targeting the AdipoRon-AdipoR2-ULK/p-ULK1 axis may represent a new therapeutic strategy for PTC.

Circ_BACH2 affects the malignant biological behavior of papillary thyroid cancer by regulating miR-370-3p

Objective: To investigate the influence of circ_BACH2 on the malignant biological behavior of papillary thyroid cancer and its molecular mechanism. Methods: Cancer tissues and paracancer tissues of 51 patients with papillary thyroid carcinoma from the Fourth Central Hospital of Tianjin between 2017 and 2019 were collected. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of circ_BACH2, miR-370-3p and G protein coupled receptor kinase interacting factor 1 (GIT1) mRNA in tissues and cells; flow cytometry to detect cell apoptosis and cell cycle; plate clone formation experiment to detect the number of cell clones; cell counting kit 8 (CCK-8) to detect cell proliferation; Transwell array to detect cell migration and invasion; western blot to detect protein expressions; dual luciferase report experiment to detect the targeting relationship between circ_BACH2, miR-370-3p and GIT1; the nude mouse tumor formation experiment to detect the effect of circ_BACH2 on tumors in mice. Results: Compared with adjacent tissues, the expressions of circ_BACH2 and GIT1 in papillary thyroid cancer tissues was increased, while the expression of miR-370-3p was decreased. Compared with Nthy-ori3-1 cells, the expressions of circ_BACH2 in papillary thyroid cancer cells TPC-1 and SW579 were increased, the mRNA and protein levels of GIT1 were increased, miR-370-3p expression was decreased. The expression level of GIT1 mRNA was negatively correlated with that of miR-370-3p (r=-0.634), and the expression level of circ_BACH2 was positively correlated with that of GIT1 (r=0.635). The expression level of circ_BACH2 was negatively correlated with that of miR-370-3p (r=-0.394, P＜0.05). Circ_BACH2 and miR-370-3p has a binding site at the 3' UTR of GIT1. After knocking down circ_BACH2, the proportion of G0/G1 cells in papillary thyroid cancer cells TPC-1 and SW579 was increased, the proportion of S-phase cells was decreased and the proportion of G2/M-phase cells did not change significantly. The cell absorbance value was lower than that in si-NC group. The number of cell clone formation was decreased (43±5 vs 100±6, 54±8 vs 100±9); the cell apoptosis rate was increased [(19.60±2.40)% vs (4.30±0.20)%, (18.10±2.10)% vs (5.10±0.23)%]; cell migration number was decreased (61±7 vs 134±15, 58±6 vs 112±11), the invasion number was also decreased (45±6 vs 113±11, 47±4 vs 92±9); the expressions of Snail and Twist1 were decreased, and the expression of E-cadherin was increased (P＜0.000). Inhibition of miR-370-3p expression reversed the effect of circ_BACH2 knockdown on proliferation, migration, invasion and apoptosis of thyroid papillary cancer cells. Overexpression of GIT1 reversed the effects of overexpression of miR-370-3p on proliferation, migration, invasion and apoptosis of thyroid papillary cancer cells. Mice injected with TPC-1 cells stably transfected with sh-circ_BACH2 showed a reduction in tumor volume [(535±91) mm3 vs (857±114) mm3] after 35 days of culture; tumor weight was decreased [(0.62±0.13) mg vs (1.06±0.15) mg, P＜0.05]; the expressions of circ_BACH2 and GIT1 were decreased, and the expression of miR-370-3p was increased in nude mouse tumor tissue. Conclusion: Silencing circ_BACH2 may inhibit the proliferation, migration and invasion of papillary thyroid cancer cells in vitro, promote cell apoptosis, and inhibit tumor growth in vivo through targeted regulation of miR-370-3p/GIT1.

PRDM1 promotes the ferroptosis and immune escape of thyroid cancer by regulating USP15-mediated SELENBP1 deubiquitination.

The deubiquitinating enzyme Ubiquitin-specific peptidase 15 (USP15) is upregulated in various cancers and promotes tumor progression by increasing the expression of several oncogenes. This project is designed to explore the role and mechanism of USP15 in thyroid cancer (TC) progression. Selenium-binding protein 1 (SELENBP1), USP15, CCL2/5, CXCL10/11, IL-4, and TGF-β1 mRNA levels were detected using real-time quantitative polymerase chain reaction (RT-qPCR). SELENBP1, USP15, GPX4, IL-10, Arg-1, Granzyme B, TNF-α, and PR domain zinc finger protein 1 (PRDM1) protein levels were examined by western blot assay. Fe+ level, malondialdehyde (MDA), and lipid-ROS levels were determined using special kits. The proportion of CD11b+CD206+ positive cells was detected using a flow cytometry assay. The role of SELENBP1 on TC cell growth was examined using a xenograft tumor model in vivo. After GeneMANIA prediction, the interaction between USP15 and SELENBP1 was verified using Co-immunoprecipitation (CoIP) assay. The binding between PRDM1 and USP15 promoter was predicted by JASPAR and validated using Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. SELENBP1 was increased in TC subjects and cell lines, and its knockdown repressed TC cell proliferation, migration, invasion, immune escape, and induced ferroptosis in vitro, as well as blocked tumor growth in vivo. In mechanism, USP15 interacted with SELENBP1 and maintained its stabilization by removing ubiquitin. Meanwhile, the upregulation of USP15 was induced by the transcription factor PRDM1. USP15 transcriptionally mediated by PRDM1 might boost TC cell malignant behaviors through deubiquitinating SELENBP1, providing a promising therapeutic target for TC treatment.

Iron oxide nanoparticles of Cystoseira sp. Sugar alcohol treat MRSA and thyroid gland cancer

PurposeMethicillin-resistant Staphylococcus aureus (MRSA) infections are emerging as a cause of suppurative thyroiditis. The resistance to several antibiotics and finding treatment has grown more difficult. Hence, the purpose of this study was to examine biosynthesized iron oxide nanostructures’ antimicrobial activity as well as their cytotoxicity on normal and thyroid cancer cells. MethodsBy using the sugar alcohols of Cystoseira sp., the authors synthesized the advanced biosynthesis of iron oxide nanoparticles (COINs). An agar-well diffusion method and a broth dilution method were used to investigate COINs’ antimicrobial activity against MRSA isolates. However, their cytotoxicity against normal and thyroid cancer cell lines was determined by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. ResultsA GC–MS analysis of the dried Cystoseira sp. extract revealed a high percentage of D-mannitol, which is essential for the synthesis of spherical nanoparticles with a mean average size of 5.8 ± 0.8 nm. The COINs showed a higher inhibition zone (9–15 mm) for 66.6 % of MRSA isolates, and the MIC of COINs was 256 μg/ml. The cell wall of these bacteria inhabits the absorption of COINs. As a result, a large concentration of COINs is required to restrict bacterial growth. Moreover, COINs have cytotoxicity on thyroid cancer cell proliferation and normal thyroid cell lines at IC50s of 1.71 ± 0.1 and 25.9 ± 1.6 μg/ml, respectively. This can be due to the negative charge of sugar alcohols, which affect protein absorption and subsequent biological behaviors. ConclusionThe promising findings of this study are in favor of the creation of very small iron oxide nanostructures for therapy.

Investigating potential mechanisms of vitamin D against thyroid cancer via network pharmacology and experimental validation.

Thyroid cancer (TC) is one of the most common endocrine malignancies worldwide. Increasing evidence suggests that vitamin D (VD) has potential benefits in the treatment of TC. However, evidence regarding the targets and molecular mechanisms of VD in TC remains limited. In this study, we conducted network pharmacology, molecular docking, and experimental evaluation to explore the target genes, biological functions, and signaling pathways involved in this process. Network analysis revealed 77 potential target genes of VD against TC, and four hub target genes were identified: ESR1, KIT, CCND1, and PGR. Furthermore, we identified the biological processes (BP) and signaling pathways involving these potential target genes, and then determined the possible interaction between the hub targets and VD through molecular docking. Finally, through invitro experiments, we found that VD effectively inhibits the proliferation of TC cells and downregulates the expression of the ESR1 gene. In conclusion, the effects of VD against TC involve multiple biological targets, BP, and signaling pathways. These findings provide scientific evidence for the application of VD in the treatment of TC.

C1GALT1 induces the carcinogenesis of thyroid cancer through regulation by miR-141-3p and GLUT1

Core 1 β 1,3-galactosyltransferase 1 (C1GALT1) acts as an important glycosyltransferase in the occurrence and development of tumor glycosylation. However, the regulatory mechanisms of C1GALT1 in thyroid cancer (TC) is still unclear. In this study, we discovered that the expression level of C1GALT1 was significantly increased in thyroid adenocarcinoma tissues and cell lines (p < 0.01). Meanwhile, gene silencing of C1GALT1 inhibited the proliferation (CCK-8 assay), migration (wound healing), and invasion (Transwell) of TC cells (p < 0.05). Further investigation indicated that miR-141-3p had a negative correlation with C1GALT1 and suppressed cancer carcinogenesis in TC cells. Moreover, we first found that glucose transporter 1 (GLUT1) was a downstream element of C1GALT1 and was positively correlated with C1GALT1 levels in TC. The GLUT1 could reverse the inhibitory effects of siRNA C1GALT1 on cell development (p < 0.05). These data suggest that the miR-141-3p/C1GALT1/GLUT1 axis plays an essential role during TC progression and may be a probable biomarker or therapeutic target for thyroid cancer patients.

Bergapten attenuates human papillary thyroid cancer cell proliferation by triggering apoptosis and the GSK-3β, P13K and AKT pathways.

Over the past few decades, thyroid cancer (TC) incidence has steadily increased globally. The most common TC is human papillary thyroid carcinoma (PTC), which is poorly responsive to the current treatments. Hence, finding a successful therapeutic is urgently required. Bergapten (BG) is a furanocoumarin, a natural psoralen derivative isolated from numerous species of citrus and bergamot oil that has demonstrated anti-tumor activity. However, there are no reports available on the efficacy of BG on PTC cells. The current research investigated the anti-cancer activity of BG on human BCPAP cells, with cytotoxicity and apoptosis evaluated using MTT assay, AO/EB, DAPI, PI, ELISA, mRNA, and western blot. Bergapten (control group, 10 μM/mL and 15 μM/mL) inhibited PTC cell proliferation and stimulated apoptosis by enhancing Bax and caspase and reducing Bcl-2, cyclin-D1, c-myc, and survivin in a dose-dependent manner. Furthermore, BG expressively attenuated PI3K/AKT/GSK-3β signaling, creating an uneven Bax/Bcl-2 ratio that triggered Cyt-c, caspase cascade and apoptosis in human PTC cells. Our findings emphasize that BG has the potential to be used as a protective natural remedy for human PTC cells.

Antitumor activity of extracellular signal-regulated kinases 1/2 inhibitor BVD-523 (ulixertinib) on thyroid cancer cells.

This study aimed to investigate BVD-523 (ulixertinib), an adenosine triphosphate (ATP)-dependent extracellular signal-regulated kinases 1/2 inhibitor, for its antitumor potential in thyroid cancer. Ten thyroid cancer cell lines known to carry mitogen-activated protein kinase (MAPK)-activated mutations, including v-Raf murine sarcoma viral oncogene homolog B (BRAF) and rat sarcoma virus (RAS) mutations, were examined. Cells were exposed to a 10-fold concentration gradient ranging from 0 to 3000 nM for 5 days. The half-inhibitory concentration was determined using the Cell Counting Kit-8 assay. Following BVD-523 treatment, cell cycle analysis was conducted using flow cytometry. In addition, the impact of BVD-523 on extracellular signal-regulated kinase (ERK)- dependent ribosomal S6 kinase (RSK) activation and the expression of cell cycle markers were assessed through western blot analysis. BVD-523 significantly inhibited thyroid cancer cell proliferation and induced G1/S cell cycle arrest dose-dependently. Notably, cell lines carrying MAPK mutations, especially those with the BRAF V600E mutation, exhibited heightened sensitivity to BVD-523's antitumor effects. Furthermore, BVD-523 suppressed cyclin D1 and phosphorylated retinoblastoma protein expression, and it robustly increased p27 levels in an RSK-independent manner. This study reveals the potent antitumor activity of BVD-523 against thyroid cancer cells bearing MAPK-activating mutations, offering promise for treating aggressive forms of thyroid cancer.

Targeting glutamine metabolism exhibits anti-tumor effects in thyroid cancer

BackgroundEffective treatment for patients with advanced thyroid cancer is lacking. Metabolism reprogramming is required for cancer to undergo oncogenic transformation and rapid tumorigenic growth. Glutamine is frequently used by cancer cells for active bioenergetic and biosynthetic needs. This study aims to investigate whether targeting glutamine metabolism is a promising therapeutic strategy for thyroid cancer.MethodsThe expression of glutaminase (GLS) and glutamate dehydrogenase (GDH) in thyroid cancer tissues was evaluated by immunohistochemistry, and glutamine metabolism-related genes were assessed using real time-qPCR and western blotting. The effects of glutamine metabolism inhibitor 6-diazo-5-oxo-l-norleucine (DON) on thyroid cancer cells were determined by CCK-8, clone formation assay, Edu incorporation assay, flow cytometry, and Transwell assay. The mechanistic study was performed by real time-qPCR, western blotting, Seahorse assay, and gas chromatography–mass spectrometer assay. The effect of DON prodrug (JHU-083) on thyroid cancer in vivo was assessed using xenograft tumor models in BALB/c nude mice.ResultsGLS and GDH were over-expressed in thyroid cancer tissues, and GLS expression was positively associated with lymph-node metastasis and TNM stage. The growth of thyroid cancer cells was significantly inhibited when cultured in glutamine-free medium. Targeting glutamine metabolism with DON inhibited the proliferation of thyroid cancer cells. DON treatment did not promote apoptosis, but increased the proportion of cells in the S phase, accompanied by the decreased expression of cyclin-dependent kinase 2 and cyclin A. DON treatment also significantly inhibited the migration and invasion of thyroid cancer cells by reducing the expression of N-cadherin, Vimentin, matrix metalloproteinase-2, and matrix metalloproteinase-9. Non-essential amino acids, including proline, alanine, aspartate, asparagine, and glycine, were reduced in thyroid cancer cells treated with DON, which could explain the decrease of proteins involved in migration, invasion, and cell cycle. The efficacy and safety of DON prodrug (JHU-083) for thyroid cancer treatment were verified in a mouse model. In addition to suppressing the proliferation and metastasis potential of thyroid cancer in vivo, enhanced innate immune response was also observed in JHU-083-treated xenograft tumors as a result of decreased expression of cluster of differentiation 47 and programmed cell death ligand 1.ConclusionsThyroid cancer exhibited enhanced glutamine metabolism, as evidenced by the glutamine dependence of thyroid cancer cells and high expression of multiple glutamine metabolism-related genes. Targeting glutamine metabolism with DON prodrug could be a promising therapeutic option for advanced thyroid cancer.