Apoptosis In Thyroid Cancer Cells Research Articles

Human epidermal growth factor receptor 2(Her2)-targeted pH-responsive MR/NIRF bimodal imaging-mediated nano-delivery system for the diagnosis and treatment of undifferentiated thyroid cancer.

Undifferentiated thyroid cancer (ATC) is highly malignant and does not respond well to sorafenib (SRF) treatment owing to the lack of specificity of SRF targeting. Drug delivery nanosystems can improve the efficiencies of drug in treating various cancer types. However, many conventional drug delivery nanosystems lack targeting and exhibit unresponsive drug release. Therefore, we developed a pH-responsive nano-targeted drug delivery systems using human serum albumin (HSA) as a carrier to generate manganese dioxide (MnO2)@HSA nanoparticles (NPs), then encapsulated SRF and the fluorescent dye indocyanine green (ICG) and finally modifyed the targeting antibody pertuzumab in the outer layer of the nano complexes, resulting in SRF/ICG/MnO2@HSA-pertuzumab (HISMP) NPs. This system targets human epidermal growth factor receptor 2 on the cell membrane surface of thyroid cancer cells and is designed to accumulate at tumor sites. Then, pH-responsive release of divalent manganese ions, ICG, and SRF enables magnetic resonance/fluorescence (MR/NIRF) dual-modality imaging and precise drug delivery for diagnostic and therapeutic integration. Various characterization analyses including transmission electron microscopy, Fourier infrared spectroscopy, and particle size analysis confirm that we successfully synthesized HISMP NPs with a diameter of 150.709nm. The results of CCK8 cytotoxicity and apoptosis assays show that HISMP NPs exhibited high cytotoxicity and induce apoptosis in thyroid cancer cells. In vivo MR/NIRF imaging experiments confirmed that the HISMP NPs specifically aggregated at tumor sites and have good in vivo MR/NIRF imaging ability and effective anti-tumor activity. The nano-delivery system is expected to provide a theoretical foundation for the efficient ATC diagnosis and therapy.

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.

TERT upstream promoter methylation regulates TERT expression and acts as a therapeutic target in TERT promoter mutation-negative thyroid cancer

BackgroundDNA hypermethylation and hotspot mutations were frequently observed in the upstream and core promoter of telomerase reverse transcriptase (TERT), respectively, and they were associated with increased TERT expression and adverse clinical outcomes in thyroid cancer. In TERT promoter mutant cancer cells, the hypomethylated TERT mutant allele was active and the hypermethylated TERT wild-type allele was silenced. However, whether and how the upstream promoter methylation regulates TERT expression in TERT mutation-negative cells were largely unknown.MethodsDNA demethylating agents 5-azacytidine and decitabine and a genomic locus-specific demethylation system based on dCas9-TET1 were used to assess the effects of TERT upstream promoter methylation on TERT expression, cell growth and apoptosis of thyroid cancer cells. Regulatory proteins binding to TERT promoter were identified by CRISPR affinity purification in situ of regulatory elements (CAPTURE) combined with mass spectrometry. The enrichments of selected regulatory proteins and histone modifications were evaluated by chromatin immunoprecipitation.ResultsThe level of DNA methylation at TERT upstream promoter and expression of TERT were significantly decreased after treatment with 5-azacytidine or decitabine in TERT promoter wild-type thyroid cancer cells. Genomic locus-specific demethylation of TERT upstream promoter induced TERT downregulation, along with cell apoptosis and growth inhibition. Consistently, demethylating agents sharply inhibited the growth of thyroid cancer cells harboring hypermethylated TERT but had little effect on cells with TERT hypomethylation. Moreover, we identified that the chromatin remodeling protein CHD4 binds to methylated TERT upstream promoter and promotes its transcription by suppressing the enrichment of H3K9me3 and H3K27me3 at TERT promoter.ConclusionsThis study uncovered the mechanism of promoter methylation mediated TERT activation in TERT promoter mutation-negative thyroid cancer cells and indicated TERT upstream promoter methylation as a therapeutic target for thyroid cancer.

LINC00115 aggravates thyroid cancer progression by targeting miR-489-3p, which downregulates EVA1A to regulate the Hippo signaling pathway

LINC00115 has been documented to regulate many different cancers; however, its function in thyroid cancer (THCA) remains unexplored. Therefore, we examined the effects of LINC00115 on THCA and the associated molecular mechanisms. In THCA cell lines and tumor samples, the expression levels of LINC00115, miR-489-3p, and EVA1A were analyzed by qRT-PCR along with respective controls. Cell viability, migration, and apoptosis were analyzed by employing CCK-8, transwell, and western blotting assays, respectively. Xenograft experiments were done to assess in vivo tumor growth. The interaction among LINC00115, miR-489-3p, and EVA1A was tested using RNA-binding protein immunoprecipitation and luciferase assays. Key proteins of the Hippo signaling pathway were ascertained by western blotting. The outcomes elucidated that LINC00115 was overexpressed in THCA cell lines and tumor tissues. LIN00115 knockdown reduced in vitro proliferation and migration but facilitated apoptosis in THCA cells and inhibited in vivo tumor growth. The target of LINC00115 was miR-489-3p, which binds to EVA1A in THCA. Functional assays revealed that miR-489-3p inhibition boosted THCA cell proliferation and migration, but hindered apoptosis. However, EVA1A knockdown resulted in the opposite effects via the Hippo signaling pathway. Additionally, miR-489-3p inhibition partially negated the effects of LINC00115 knockdown in THCA cells, and EVA1A knockdown remarkably impeded the effects of miR-489-3p inhibition in THCA cells. Thus, LINC00115 knockdown suppressed THCA carcinogenesis via targeting miR-489-3p, which regulates EVA1A expression and affects the Hippo signaling pathway.

GPX4 inhibits apoptosis of thyroid cancer cells through regulating the FKBP8/Bcl-2 axis.

GPX4 has attracted much attention as a key molecule of cell ferroptosis, but its role in cell apoptosis is rarely reported, and its role in apoptosis of thyroid cancer (TC) cell has not been reported. The analysis of TCGA database showed that both GPX4 and FKBP8 were highly expressed in TC tumor tissues; The expression of GPX4 and FKBP8 were positively correlated. The immunohistochemical analysis further confirmed that GPX4 and FKBP8 were highly expressed in TC tumor tissues. In addition, the high expression of GPX4 and FKBP8 were both significantly correlated with the poor prognosis of TC. Silencing GPX4 significantly inhibited the proliferation, induced apoptosis of TC cells, and reduced tumor growth in mice. The co-immunoprecipitation assay revealed a physical interaction between GPX4 and FKBP8 observed in the TC cells. Knockdown of FKBP8 significantly inhibited the proliferation and induced apoptosis of TC cells. Rescue experiments suggested that knockdown of FKBP8 could reverse the strengthens of cell proliferation and apoptosis and the higher expression of FKBP8 and Bcl-2 caused by overexpression of GPX4. Our results suggest that the GPX4/FKBP8/Bcl-2 axis promotes TC development by inhibiting TC cell apoptosis, which provides potential molecular targets for TC therapeutic strategies.

MiR-138-5p Inhibits Thyroid Cancer Cell Growth and Stemness by Targeting TRPC5/Wnt/β-Catenin Pathway.

MicroRNAs play a key role in the pathogenesis of many types of cancer, including thyroid cancer (TC). MiR-138-5p has been confirmed to be abnormally expressed in TC tissues. However, the role of miR-138-5p in TC progression and its potential molecular mechanism need to be further explored. In this study, quantitative real-time PCR was used to examine miR-138-5p and TRPC5 expression, and western blot analysis was performed to examine the protein levels of TRPC5, stemness-related markers, and Wnt pathway-related markers. Dual-luciferase reporter assay was used to assess the interaction between miR-138-5p and TRPC5. Cell proliferation, stemness, and apoptosis were examined using colony formation assay, sphere formation assay, and flow cytometry. Our data showed that miR-138-5p could target TRPC5 and its expression was negatively correlated with TRPC5 expression in TC tumor tissues. MiR-138-5p decreased proliferation, stemness, and promoted gemcitabine-induced apoptosis in TC cells, and this effect could be reversed by TRPC5 overexpression. Moreover, TRPC5 overexpression abolished the inhibitory effect of miR-138-5p on the activity of Wnt/β-catenin pathway. In conclusion, our data showed that miR-138-5p suppressed TC cell growth and stemness via the regulation of TRPC5/Wnt/β-catenin pathway, which provided some guidance for studying the potential function of miR-138-5p in TC progression.

Sodium-iodide symporter and its related solute carriers in thyroid cancer.

The solute carrier (SLC) family is a large group of membrane transport proteins. Their dysfunction plays an important role in the pathogenesis of thyroid cancer. The most well-known SLC is the sodium-iodide symporter (NIS), also known as sodium/iodide co-transporter or solute carrier family 5 member 5 (SLC5A5) in thyroid cancer. The dysregulation of NIS in thyroid cancer is well documented. The role of NIS in the uptake of iodide is critical in the treatment of thyroid cancer, radioactive iodide (RAI) therapy in particular. In addition to NIS, other SLC members may affect the autophagy, proliferation, and apoptosis of thyroid cancer cells, indicating that an alteration in SLC members may affect different cellular events in the evolution of thyroid cancer. The expression of the SLC members may impact the uptake of chemicals by the thyroid, suggesting that targeting SLC members may be a promising therapeutic strategy in thyroid cancer.

MicroRNA-181b-5p Facilitates Thyroid Cancer Growth via Targeting Programmed Cell Death 4.

To explore the potential mechanism of microRNA (miR)-181b-5p promoting the progression of thyroid cancer (TC) by targeting programmed cell death 4 (PDCD4). Analysis of miR-181b-5p and PDCD4 expression in TC was performed. The impact of miR-181b-5p and PDCD4 on proliferation, migration, invasion, and apoptosis of TC cells was examined. The binding relationship between miR-181b-5p and PDCD4 was predicted and verified. miR-181b-5p was up-regulated in TC, while PDCD4 was down-regulated. Down-regulating miR-181b-5p or up-regulating PDCD4 inhibited the proliferation, migration, and invasion of TC cells, and promoted cell apoptosis. PDCD4 was the downstream target of miR-181b-5p, and down-regulation of PDCD4 counteracted the inhibitory effect of down-regulation of miR-181b-5p on the proliferation, migration, and invasion of TC cells and the promoting effect on apoptosis. miR-181b-5p inhibits the proliferation, migration, and invasion of TC cells and promotes cell apoptosis by targeting PDCD4.

Maslinic acid induces apoptosis in thyroid cancer cells via endoplasmic reticulum stress

Maslinic acid induces apoptosis in thyroid cancer cells via endoplasmic reticulum stress

Network pharmacology-based prediction and experimental verification of the involvement of the PI3K/Akt pathway in the anti-thyroid cancer activity of crocin

Crocin, a unique water-soluble carotenoid extracted from saffron, is known to exert anticancer activity against various cancer types, including thyroid cancer (TC). However, the detailed mechanism underlying the anticancer effect of crocin in TC needs further exploration. Targets of crocin and targets associated with TC were acquired from public databases. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed using DAVID. Cell viability and proliferation were assessed using MMT and EdU incorporation assays, respectively. Apoptosis was assessed using TUNEL and caspase-3 activity assays. The effect of crocin on phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) was explored by western blot analysis. A total of 20 overlapping targets were identified as candidate targets of crocin against TC. GO analysis showed that these overlapping genes were significantly enriched in the positive regulation of cell proliferation. KEGG results showed that the PI3K/Akt pathway was involved in the effect of crocin against TC. Crocin treatment inhibited cell proliferation and promoted apoptosis in TC cells. Moreover, we found that crocin inhibited the PI3K/Akt pathway in TC cells. 740Y–P treatment reversed the effects of crocin on TC cells. In conclusion, crocin suppressed proliferation and elicited apoptosis in TC cells via inactivation of the PI3K/Akt pathway.

Abstract 4853: Evaluating the role of melatonin in thyroid cancer cell (MDA-T41) apoptosis and metabolism modulation

Abstract Melatonin, a hormone produced by the pineal gland, is typically known for its modulation of a number of physiological functions, alongside its ability to synchronize the sleep-wake rhythms. In recent years, however, its interactions with cancerous cells and role in prevention and treatment have been increasingly studied. It has been demonstrated that melatonin can improve the efficacy of chemotherapeutic drugs and directly inhibit tumorigenesis in experimental models of neoplasia. In addition, while melatonin typically displays anti-apoptotic effects in normal cells, it holds pro-apoptotic effects in cancer cells. Despite this, the mechanisms by which melatonin affects cell death and metabolism remain unclear due to the seeming difference from cell to cell. We aim to better understand the role of melatonin in regulating thyroid cancer cell apoptosis and metabolism. The MDA-T41 thyroid cancer cell line was cultured with varying quantities of melatonin. Steady volumes of staurosporine (an inductor of apoptotic cell death) were applied to cultures, and cell death levels were subsequently measured using the Realtime-Glo Annexin V Apoptosis and Necrosis assay. Our results showed that melatonin provided anti-apoptotic effects to MDA-T41 cells treated with staurosporine. Both apoptosis and necrosis were reduced by 50% in melatonin-treated cells 24 hours after staurosporine-induced cell death. Our next steps will be to evaluate the mechanisms and further signaling pathways involved in this apoptosis inhibition through Bcl-2 and p53 protein expression. Citation Format: Angela Huang, Daniel Sanches. Evaluating the role of melatonin in thyroid cancer cell (MDA-T41) apoptosis and metabolism modulation. [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 4853.

Prognostic subtypes of thyroid cancer was constructed based on single cell and bulk-RNA sequencing data and verified its authenticity.

There has been an increase in the mortality rate of thyroid cancer (THCA), which is the most common endocrine malignancy. We identified six distinct cell types in the THAC microenvironment by analyzing single-cell RNA sequencing (Sc-RNAseq) data from 23 THCA tumor samples, indicating high intratumoral heterogeneity. Through re-dimensional clustering of immune subset cells, myeloid cells, cancer-associated fibroblasts, and thyroid cell subsets, we deeply reveal differences in the tumor microenvironment of thyroid cancer. Through an in-depth analysis of thyroid cell subsets, we identified the process of thyroid cell deterioration (normal, intermediate, malignant cells). Through cell-to-cell communication analysis, we found a strong link between thyroid cells and fibroblasts and B cells in the MIF signaling pathway. In addition, we found a strong correlation between thyroid cells and B cells, TampNK cells, and bone marrow cells. Finally, we developed a prognostic model based on differentially expressed genes in thyroid cells from single-cell analysis. Both in the training set and the testing set, it can effectively predict the survival of thyroid patients. In addition, we identified significant differences in the composition of immune cell subsets between high-risk and low-risk patients, which may be responsible for their different prognosis. Through in vitro experiments, we identify that knockdown of NPC2 can significantly promote thyroid cancer cell apoptosis, and NPC2 may be a potential therapeutic target for thyroid cancer. In this study, we developed a well-performing prognostic model based on Sc-RNAseq data, revealing the cellular microenvironment and tumor heterogeneity of thyroid cancer. This will help to provide more accurate personalized treatment for patients in clinical diagnosis.

The curcumin analogue PAC has potent anti-anaplastic thyroid cancer effects

Anaplastic thyroid carcinoma (ATC) is the rarest type of thyroid cancer, but is the common cause of death from these tumors. The aggressive behavior of ATC makes it resistant to the conventional therapeutic approaches. Thus, the present study was designed to evaluate the anti-ATC efficacy of the piperidone analogue of curcumin (PAC). We have shown that PAC induces apoptosis in thyroid cancer cells in a time-dependent fashion through the mitochondrial pathway. Immunoblotting analysis revealed that PAC suppressed the epithelial-to-mesenchymal transition (EMT) process in ATC cells by upregulating the epithelial marker E-cadherin and reducing the level of the mesenchymal markers N-cadherin, Snail, and Twist1. This anti-EMT effect was confirmed by showing PAC-dependent inhibition of the proliferation and migration abilities of ATC cells. Furthermore, PAC inhibited the AKT/mTOR pathway in ATC cells. Indeed, PAC downregulated mTOR and its downstream effectors p70S6K and 4E-BP1 more efficiently than the well-known mTOR inhibitor rapamycin. In addition to the promising in vitro anticancer efficacy, PAC significantly suppressed the growth of humanized thyroid tumor xenografts in mice. Together, these findings indicate that PAC could be considered as promising therapeutic agent for anaplastic thyroid carcinomas.

The prognostic and immune significance of C15orf48 in pan-cancer and its relationship with proliferation and apoptosis of thyroid carcinoma.

C15orf48 was recently identified as an inflammatory response-related gene; however there is limited information on its function in tumors. In this study, we aimed to elucidate the function and potential mechanism of action of C15orf48 in cancer. We evaluated the pan-cancer expression, methylation, and mutation data of C15orf48 to analyze its clinical prognostic value. In addition, we explored the pan-cancer immunological characteristics of C15orf48, especially in thyroid cancer (THCA), by correlation analysis. Additionally, we conducted a THCA subtype analysis of C15orf48 to determine its subtype-specific expression and immunological characteristics. Lastly, we evaluated the effects of C15orf48 knockdown on the THCA cell line, BHT101, by in vitro experimentation. The results of our study revealed that C15orf48 is differentially expressed in different cancer types and that it can serve as an independent prognostic factor for glioma. Additionally, we found that the epigenetic alterations of C15orf48 are highly heterogeneous in several cancers and that its aberrant methylation and copy number variation are associated with poor prognosis in multiple cancers. Immunoassays elucidated that C15orf48 was significantly associated with macrophage immune infiltration and multiple immune checkpoints in THCA, and was a potential biomarker for PTC. In addition, cell experiments showed that the knockdown of C15orf48 could reduce the proliferation, migration, and apoptosis abilities of THCA cells. The results of this study indicate that C15orf48 is a potential tumor prognostic biomarker and immunotherapy target, and plays an essential role in the proliferation, migration, and apoptosis of THCA cells.

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.

Contribution of microRNA-30d to the prevention of the thyroid cancer occurrence and progression: mechanism and implications.

Thyroid cancer is a major endocrine tumor and represents an emerging health problem worldwide. MicroRNAs (miRNAs) have been addressed to participate in the pathogenesis and progression of thyroid cancer. However, it remains largely unknown what functions miR-30d may exert on thyroid cancer. This study, herein, aimed to identify the functional significance and machinery of miR-30d in the progression of thyroid cancer. MiR-30b presented aberrant low expression and ubiquitin-specific protease 22 (USP22) exhibited aberrant high expression in thyroid cancer tissues and cells. The current study proposed the possible machinery that miR-30d could target and negatively regulate USP22. Additionally, USP22 could enhance the stability of SIRT1 by inducing deubiquitination which consequently contributed to FOXO3a deacetylation-induced PUMA repression. Responding to the gain- or loss-of-function of miR-30d and/or USP22, behaviors of thyroid cancer cells were altered. Accordingly, miR-30d inhibited proliferation and promoted apoptosis of thyroid cancer cells by suppressing USP22 through SIRT1/FOXO3a/PUMA axis. The effects of miR-30d and USP22-mediated SIRT1/FOXO3a/PUMA axis on thyroid tumorigenesis were finally validated in murine models. We ultimately confirmed the anti-proliferative and pro-apoptotic effect of miR-30d via suppressing USP22 through in vivo findings. Conclusively, our findings highlight that the occurrence and progression of thyroid cancer can be suppressed by miR-30d-mediated inhibition of USP22 via the SIRT1/FOXO3a/PUMA axis, which provides a attractive therapeutic target for thyroid cancer treatment.

LncRNA EGFEM1P promotes thyroid cancer progression by acting as an miR-369-3p sponge and upregulating TCF4.

Thyroid cancer is the most commonly diagnosed endocrine cancer, with the incidence of 14.42 per 100,000 person-years in 2010-2013. It is important to conduct an in-depth exploration into the molecular mechanisms of thyroid cancer, providing insights into the improvements of therapy. Long non-coding RNAs (lncRNAs) act as oncogenes or tumor suppressors in thyroid cancer by sponging microRNAs (miRNAs), however, the functions of numerous lncRNAs are still unknown. In the present study, via the comprehensive analysis of microarray data derived from papillary thyroid tumors and the RNA sequencing of thyroid tumors from The Cancer Genome Atlas database, EGF like and EMI domain containing 1 (EGFEM1P) expression levels in papillary thyroid tumors and normal adjacent tissues were explored. Reverse transcription-quantitative PCR was used to detect EGFEM1P, microRNA (miR)-369-3p and T cell factor 4 (TCF4) expression levels. Western blotting was used to detect TCF4 protein and cleaved caspase-3/8 expression levels. Cell proliferative ability and apoptosis were assessed using the Cell Counting Kit-8 assay and flow cytometry, respectively. The interactions between EGFEM1P and miR-369-3p, and miR-369-3p and TCF4, were determined using the dual-luciferase reporter assay. The results demonstrated that EGFEM1P was upregulated in papillary thyroid tumors and thyroid cancer cells compared with normal adjacent tissues and human normal thyroid epithelial Nthy-ori 3-1 cell line. In the examined thyroid cancer cells, EGFEM1P was demonstrated to interact with miR-369-3p and decreased miR-369-3p expression levels. Thereafter, TCF4 was determined to be a target gene of miR-369-3p and EGFEM1P promoted TCF4 expression via regulating miR-369-3p expression levels. At last, it was found that EGFEM1P expression promoted rapid cell proliferation and inhibited cell apoptosis in thyroid cancer cells via acting as a miR-369-3p sponge. In conclusion EGFEM1P promoted thyroid cancer progression via acting as a sponge of the miR-369-3p/TCF4 axis.

KIF11 Is a Promising Therapeutic Target for Thyroid Cancer Treatment.

Objective To assess KIF11 expression in human thyroid tumor tissues and further evaluate its involvement in thyroid cancer. Methods The expression of KIF11 in 71 cases of thyroid carcinoma as well as corresponding tissues was detected by the immunohistochemical (IHC) method. Patients were divided into the high KIF11 expression as well as low expression groups based on the staining levels. In addition, to study the relationship between the expression of KIF11 as well as clinicopathological features, the effects of KIF11 were detected on the proliferation, apoptosis, and cell cycle of two types of thyroid cancer cells, TPC-1 and KTC-1, through colony formation assays, MTT assays, and FCM assays, respectively. We further assessed the potential effects of KIF11 on tumor growth using an animal model. Results The significantly high expression of KIF11 in thyroid tumor tissues was revealed, and the correlations between KIF11 expression levels as well as clinical pathological features (T stage and intraglandular dissemination) of patients were revealed. We further noticed that KIF11 knockdown remarkably suppressed thyroid cancer cell proliferation as well as induced cell apoptosis of thyroid cancer cells. Additionally, KIF11 contributed to tumor growth of thyroid cancer cells in mice. Conclusions We noticed the involvement of KIF11 in the progression of thyroid cancer.

MiR-221 Regulates Suppressors of Cytokine Signaling 3-Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (SOCS3-JAK2/STAT3) Pathway and Affects Thyroid Cancer Cell Proliferation and Apoptosis

Objective: Suppressors of cytokine signaling 3 (SOCS3) negatively regulates JAK-STAT signaling. Bioinformatics analysis showed a targeted relationship between miR-221 and SOCS3 mRNA 3′-UTR. This study investigated whether miR-221 regulates SOCS3 expression and affects thyroid cancer cells. Methods: Dual-luciferase reporter gene experiments verified the relationship between miR-221 and SOCS3. The tumor tissues and adjacent tissues of patients with thyroid cancer were collected to detect miR-221 and SOCS3 level. Thyroid cancer cell line KTC-1 cells were assigned into miR-NC group and miR-221 inhibitor group followed by analysis of SOCS3, p-JAK2, and p-STAT3 level by Real-time PCR, cell apoptosis and cell proliferation by flow cytometry and cell invasion by Transwell assay. Results: Compared with adjacent tissues, miR-221 level in tumor tissues was increased, and SCOS3 mRNA level was decreased. There was a targeted relationship between miR-221 and SOCS3 mRNA. MiR-221 level in KTC-1 and TPC-1 cells was increased, while SOCS3 mRNA level was decreased. MiR-221 inhibitor can significantly upregulate SOCS3 mRNA and protein in KTC-1 cells, reduce the expression of p-JAK2, p-STAT3 protein, increase cell apoptosis, and reduce cell proliferation and invasion. Conclusion: The increased miR-221 and decreased SOCS3 expression are related to thyroid cancer pathogenesis. MiR-221 can inhibit the expression of SOCS3, affect JAK-STAT signaling activity, and regulate the proliferation and apoptosis of thyroid cancer cells.

Melatonin promotes apoptosis of thyroid cancer cells via regulating the signaling of microRNA-21 (miR-21) and microRNA-30e (miR-30e)

ABSTRACT Melatonin (MEL) is an effective therapeutic choice for thyroid cancer treatment. In this study, we aimed to explored the potential effect of MEL upon the drug sensitivity of cancer cells and the according underlying mechanisms. Thyroid cancer mice were established as a control group and a MEL group to observe the in vivo effect of MEL. Tumor size and weight in nude mice were detected to evaluate the effect of MEL on tumor growth. Immunohistochemistry assay (IHC) and Western blot were performed to analyze the expression of PTEN protein in tumor cells or tumor cells. After 32 days of cancer cell implantation, MEL was found to significantly repress tumor growth in nude mice approximately by half. Moreover, MEL also suppressed tumor cell proliferation, while apparently activating the apoptosis of tumor cells. In addition, hydrogen sulfide (H2S) production was obviously elevated by MEL treatment. Mechanistically, the expression of phosphatase and tensin homolog (PTEN) was remarkably activated by MEL treatment in tumor tissues of implanted TPC-1 and BCPaP cells in nude mice. Meanwhile, MEL inhibited the expression of miR-21 and miR-30e and promoted the expression of lncRNA-cancer susceptibility candidate 7 (CASC7). Both miR-21 and miR-30e could suppress PTEN expression, while miR-21 could also inhibit the expression of lncRNA-CASC7. In conclusion, the results demonstrated that the MEL administration could downregulate the expression of miR-21 and miR-30e, which resulted in increased expression of PTEN, a pro-apoptotic tumor suppressor, to promote the apoptosis of thyroid cancer cells.