Invasion Of Thyroid Carcinoma Cells Research Articles

GNA15 facilitates the malignant development of thyroid carcinoma cells via the BTK-mediated MAPK signaling pathway.

G protein subunit alpha 15 (GNA15) is recognized as an oncogene for some cancers, however, its role in thyroid carcinoma (TC) is elusive and is investigated in this study. Concretely, bioinformatics was employed to analyze the GNA15 expression profile in TC. The effect of GNA15 on TC cell functions was examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, and Transwell assays. Expressions of extracellular regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 were determined using Western blot. The involvement of Bruton tyrosine kinase (BTK) in the mechanism of GNA15 was investigated by BTK knockdown and rescue assay. GNA15 presented an overexpression pattern in TC samples, which facilitated the viability, proliferation, migration, and invasion of TC cells; GNA15 silencing led to converse results. Ratios of p-ERK/ERK, p-JNK/JNK, and p-p38/p38 were upregulated by GNA15 overexpression. The BTK deficiency weakened the aforementioned behaviors of TC cells and blocked the MAPK signaling pathway, however, these effects were counteracted by GNA15 overexpression. Collectively, GNA15 contributes to the malignant development of TC cells by binding to BTK and thus activating the MAPK signaling pathway.

TIM3 activates the ERK1/2 pathway to promote invasion and migration of thyroid tumors.

This study aims to study the possible action mechanism of T-cell immunoglobulin and mucin domain 3 (TIM3) on the migratory and invasive abilities of thyroid carcinoma (TC) cells. GSE104005 and GSE138198 datasets were downloaded from the GEO database for identifying differentially expressed genes (DEGs). Functional enrichment analysis and protein-protein interaction (PPI) analysis were performed on the common DEGs in GSE104005 and GSE138198 datasets. Subsequently, in order to understand the effect of a common DEG (TIM3) on TC cells, we performed in vitro experiments using FRO cells. The migratory and invasive abilities of FRO cells were detected by wound scratch assay and Transwell assay. Proteins expression levels of the phosphorylated (p)-extracellular signal-regulated kinase (ERK)1/2, matrix metalloproteinase-2 (MMP-2) and MMP-9 were determined via Western blotting after ERK1/2 inhibition in TIM3-NC group and TIM3-mimic group. 316 common DEGs were identified in GSE104005 and GSE138198 datasets. These DEGs were involved in the biological process of ERK1 and ERK2 cascade. TIM3 was significantly up-regulated in TC. In vitro cell experiments showed that TIM3 could promote migration and invasion of TC cells. Moreover, TIM3 may affect the migration, invasive abilities of TC cells by activating the ERK1/2 pathway. The above results indicate that TIM3 may affect the migratory and invasive of TC cells by activating the ERK1/2 pathway.

Effect of hypoxia‑HIF‑1α‑periostin axis in thyroid cancer.

The incidence of thyroid carcinoma (TC) has exhibited a rapid increase in recent years. A proportion of TCs exhibit aggressive behavior. The present study aimed to investigate the potential role of hypoxia‑hypoxia inducible factor 1 subunit α (HIF‑1α)‑periostin axis in the progression of TC. The upregulation of periostin and HIF‑1α expression levels was detected in 95 clinical TC tissues as compared with normal thyroid tissues. Hypoxia promoted the viability and invasion of TC cells and this effect was inhibited by the downregulation of periostin. Hypoxia also induced the Warburg effect in TC and this effect was inhibited by the silencing of periostin. Further investigations revealed that hypoxia activated HIF‑1α, which in turn regulated the expression of periostin. Immunoprecipitation and dual luciferase reporter assays demonstrated that HIF‑1α upregulated the expression of periostin by binding to the promoter of periostin. On the whole, these findings suggest the existence of a hypoxia‑HIF‑1α‑periostin axis in TC and indicate the role of this axis in the progression of TC.

ML385 suppresses the proliferation, migration, and invasion of thyroid carcinoma cells by impairing aerobic glycolysis

ML385 suppresses the proliferation, migration, and invasion of thyroid carcinoma cells by impairing aerobic glycolysis

CircGLIS3 inhibits thyroid cancer invasion and metastasis through miR-146b-3p/AIF1L axis.

Studies have shown that circRNA is involved in the occurrence and development of human cancers. However, it remains unclear that the contribution of circRNA in thyroid carcinoma and its role in the process of tumorigenesis. The expression profile of circRNA-miRNA-mRNA in thyroid carcinoma was detected by RNA sequencing and verified by qRT-PCR. The characteristics of circGLIS3 were verified by RNase R and actinomycin assays, subcellular fractionation, and fluorescence in situ hybridization. The functions of circGLIS3 and AIF1L were detected by wound healing, transwell, 3D culture and Western blot. RNA Immunoprecipitation (RIP), RNA pulldown and dual-luciferase reporter assays were used to verify the target genes of circGLIS3 and downstream miRNAs. Functional rescue experiments were performed by transfecting miRNA mimics or siRNA of target genes. Finally, metastatic mouse models were used to investigate circGLIS3 function in vivo. In this study, we discovered a novel circRNA (has_circ_0007368, named as circGLIS3) by RNA sequencing. CircGLIS3 was down-regulated in thyroid carcinoma tissues and cells line, and was negatively associated with malignant clinical features of thyroid carcinoma. Functional studies found that circGLIS3 could inhibit the migration and invasion of thyroid carcinoma cells, and was related to the EMT process. Mechanistically, circGLIS3 can upregulate the expression of the AIF1L gene by acting as a miR-146b-3p sponge to inhibit the progression of thyroid carcinoma. Our study identified circGLIS3 as a novel tumor suppressor in thyroid cancer, indicating the potential of circGLIS3 as a promising diagnostic and prognostic marker for thyroid cancer.

Concurrent PIK3CA and TERT Mutation Promote the Proliferation and Invasion of Thyroid Carcinoma Cells and may be Caused by Up-regulating the Expression of GABPA/GABPB1

Our previous research demonstrated that TERT and concurrent PIK3CA mutations predict worse overall survival in patients with poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma. However, the molecular mechanism underlying the synergistic oncogenic operations of the two oncogenes is unclear. This study aimed to explore further the effect of TERT and PIK3CA co-mutation on the malignant biological phenotype of thyroid carcinoma and its possible mechanism. PIK3CA E545K mutation plasmid was transfected into thyroid anaplastic cancer cell line (C643) with TERT promoter mutation, then CCK-8 and transwell invasion assays were used to investigate the ability of cell proliferation and invasion, respectively. RT-qPCR and western blot were performed to detect the expression of PIK3CA, TERT, GABPA and GABPB1. GABPA/GABPB1 siRNA plasmid was transfected with C643 cells, then the ability of cell proliferation and invasion were identified. We also detected the expression of PIK3CA and TERT. C643 cells carry TERT promoter mutation C228T. Concurrent PIK3CA E545K and TERT mutation markedly enhanced the proliferation and invasion of C643 cell in vitro, with significantly increased mRNA/protein expression of PIK3CA, TERT, GABPA and GABPB1. Knocking down GABPA markedly inhibited cell proliferation. Knocking down of GABPB1 significantly decreased the proliferation and invasion of C643 cells, with much lower expression of PIK3CA and TERT. TERT and PIK3CA co-mutations promote the proliferation and invasion of thyroid anaplastic carcinoma cells and may be caused by up-regulating the expression of GABPA and GABPB1.

Hypomethylation-mediated overexpression of ITGA2 stimulates cell invasion and migration of thyroid carcinoma.

To study the molecular mechanism of DNA methylation-mediated ITGA2 overexpression in thyroid carcinoma (TC). First, 450K methylation data and mRNA expression profiles in TCGA-THCA dataset were downloaded from TCGA database. ITGA2 was identified as a methylation-driven gene by using R package "MethylMix". Afterwards, qRT-PCR, western blot and flow cytometry assay were performed to measure ITGA2 expression in TC cells. Methylation-specific PCR was utilized to measure promoter region methylation of ITGA2 in TC cells. Transwell and wound healing assays were carried out to assess cell invasive and migratory properties. Compared with normal cells, TC cells presented significantly increased ITGA2 expression. In addition, ITGA2 expression was controlled by DNA methylation. Hypomethylation of CpG island resulted in an increased ITGA2 expression. Hence, methylation and expression levels of ITGA2 were inversely associated. Moreover, overexpression of ITGA2 and promoter region hypomethylation facilitated cell invasive and migratory abilities in TC. These findings authenticated that promoter region hypomethylation of ITGA2 fostered ITGA2 expression as well as TC cell invasion and migration.

Cystathionine β-Synthase Regulates the Proliferation, Migration, and Invasion of Thyroid Carcinoma Cells.

Thyroid cancer is considered to be one of the most common endocrine tumors worldwide. Cystathionine β-synthase (CBS) plays a crucial role in the occurrence of several types of malignancies. And yet, the mechanism of action of CBS in the growth of thyroid carcinoma cells is still unrevealed. We found that CBS level in thyroid carcinoma tissue was higher than that in adjacent normal tissue. The overexpression of CBS enhanced the proliferation, migration, and invasion of thyroid cancer cells, while the downregulation of CBS exerted reverse effects. CBS overexpression reduced the levels of cleaved caspase-3 and cleaved poly ADP-ribose polymerase in thyroid cancer cells, whereas CBS knockdown showed reverse trends. CBS overexpression decreased reactive oxygen species (ROS) levels but increased the levels of Wnt3a and phosphorylations of phosphatidylinositol 3-kinase (PI3K), protein kinase B (PKB/AKT), mammalian target of rapamycin (mTOR), β-catenin, and glycogen synthase kinase-3 beta, while CBS knockdown exerted opposite effects. In addition, CBS overexpression promoted the growth of xenografted thyroid carcinoma, whereas CBS knockdown decreased the tumor growth by modulating angiogenesis, cell cycle, and apoptosis. Furthermore, aminooxyacetic acid (an inhibitor of CBS) dose-dependently inhibited thyroid carcinoma cell growth. CBS can regulate the proliferation, migration, and invasion of human thyroid cancer cells via ROS-mediated PI3K/AKT/mTOR and Wnt/β-catenin pathways. CBS can be a potential biomarker for diagnosing or prognosing thyroid carcinoma. Novel donors that inhibit the expression of CBS can be developed in the treatment of thyroid carcinoma.

Ubiquitin conjugating enzyme E2 C (UBE2C) may play a dual role involved in the progression of thyroid carcinoma

The present study aimed to explore the role of ubiquitin-conjugating enzyme E2 C (UBE2C) in the progress of thyroid carcinoma (THCA). We firstly explored the prognostic impact and expression level of UBE2C in THCA. Then, we performed the UBE2C knockdown and evaluated the effects on the proliferation, cell cycle distribution, apoptosis, migration, and invasion of THCA cells, as well as resistance to sorafenib. Finally, we predicted the possible pathways and explored the correlation between UBE2C with immune infiltrates. The results showed that high expression of UBE2C independently predicted a shorter disease-free survival time of THCA patients. And UBE2C also presented a better prognostic performance on the survival probability of patients. Expression analysis showed that UBE2C was statistically upregulated in THCA tissue compared with normal tissue. After UBE2C knockdown, the proliferation of THCA cells was inhibited and apoptosis was increased. These results indicated that UBE2C acted as an oncogene in THCA. However, the migration and invasion of THCA cells with UBE2C knockdown were enhanced, and the expressions of migration-related proteins were upregulated. In addition, UBE2C knockdown increased the resistance of THCA cells to sorafenib. These results implied the potential of UBE2C as a suppressor gene in THCA. The pathway analysis further predicted that metabolism-related pathways were activated in the UBE2C low expression class, and cell growth and immune-related pathways were focused on the UBE2C high expression class. Finally, we observed a significant positive relationship between UBE2C and several immune infiltrates in THCA. It followed that UBE2C high expression might play a vital role in THCA to some extent. This study revealed that UBE2C participated in the progression of THCA and may play the dual role of both oncogene and tumor suppressor gene. The detailed mechanism needed to be further investigated.

Ultrasound-targeted microbubble destruction-mediated miR-144-5p overexpression enhances the anti-tumor effect of paclitaxel on thyroid carcinoma by targeting STON2

ABSTRACT The effects of miR-144-5p and paclitaxel (PTX) on thyroid carcinoma were less explored. Thus, we investigated the effects of miR-144-5p and PTX on thyroid carcinoma. The expression and target gene of miR-144-5p in thyroid carcinoma were analyzed by bioinformatics, y qRT-PCR and dual-luciferase reporter assay. After the transfection mediated by ultrasound-targeted microbubble destruction (UTMD) or liposome, or the treatment of PTX, the viability, proliferation, migration, and invasion of thyroid carcinoma cells were detected by MTT, colony formation, wound-healing, and transwell assays. The expressions of miR-144-5p, STON2, MMP-9, E-cadherin, and N-cadherin in cells were calculated via qRT-PCR or Western blotting. After a subcutaneous-xenotransplant tumor model was established using BALB/c nude mice and further treated with PTX and UTMD-mediated miR-144-5p, the volume, weight, and Ki67 level of tumor were recorded or evaluated by immunohistochemical assays. MiR-144-5p, which was low-expressed in thyroid carcinoma, directly down-regulated STON2 level. MiR-144-5p overexpression and PTX inhibited the viability, proliferation, migration, and invasion of thyroid carcinoma cells, while miR-144-5p silencing caused the opposite results. MiR-144-5p overexpression and PTX further up-regulated E-cadherin level and down-regulated those of MMP-9 and N-cadherin in thyroid carcinoma cells. STON2 overexpression reversed the effects of miR-144-5p overexpression.. MiR-144-5p overexpression enhanced the inhibiting effect of PTX on tumor volume, weight, and Ki67 level of xenotransplant tumor, and the effects of UTMD-mediated miR-144-5p overexpression were stronger than those mediated by liposome. Collectively, UTMD-mediated miR-144-5p overexpression enhanced the anti-tumor effect of PTX on thyroid carcinoma by targeting STON2.

FOXP2 regulates the proliferation, migration, and apoptosis of thyroid carcinoma cells via Wnt/β-catenin signaling pathway

Purpose: To determine the effect of Forkhead box P2 (FOXP2) on thyroid carcinoma cell growth and metastasis.
 Methods: Expression of FOXP2 in thyroid carcinoma cells was determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot. The 3-[4,5-dimethylthiazol-2-yl]- 2,5 diphenyl tetrazolium bromide (MTT) was applied to evaluate cell viability, while cell migration and invasion were assessed by wound healing and Transwell assays, respectively. Flow cytometry and western blot were conducted to investigate cell apoptosis. The underlying mechanisms were investigated using western blot assay.
 Results: Expression of FOXP2 was lower in primary thyroid carcinoma tissues than in normal tissues based on data from the TCGA database. Similarly, FOXP2 was lower in thyroid carcinoma cells at the mRNA and protein levels. Ectopic FOXP2 expression decreased cell viability, and retarded the migration and invasion of thyroid carcinoma cells. FOXP2 overexpression in thyroid carcinoma cells led to down-regulated expression of matrix metallopeptidase (MMP) 2, MMP 9, and proliferating cell nuclear antigen (PCNA), as well as induction of cell apoptosis. Moreover, FOXP2 overexpression resulted in enhanced Bax expression while Bcl-2 was reduced. Ectopic expression of FOXP2 decreased β-catenin, c-myc, and cyclin D1 in thyroid carcinoma cells.
 Conclusion: FOXP2 suppresses the proliferation and metastasis of thyroid carcinoma cells, but promotes apoptosis through suppression of the Wnt/β-catenin signaling pathway. These results provide an insight that may lead to the development of a novel potential therapeutic strategy for treating thyroid carcinoma.

Activation of the TGF-β1/Smad signaling by KIF2C contributes to the malignant phenotype of thyroid carcinoma cells

Kinesin family member 2C (KIF2C) has been identified as a potential oncogene in various types of human cancers; however, the role of KIF2C in thyroid cancer has not yet been elucidated. Quantitative real-time polymerase chain reaction and western blotting were employed for gene expression analysis. Cell Counting Kit-8 and ethynyl-2′-deoxyuridine assays were performed to examine cell proliferation. Cell migration and invasion were assessed by wound-healing and transwell invasion assays. Results showed that KIF2C expression was upregulated in thyroid carcinoma cell lines. In addition, upregulation of KIF2C promoted the proliferation, migration, and invasion of thyroid carcinoma cells, while downregulation of KIF2C exerted the opposite effects. Overexpression of KIF2C induced the activation of transforming growth factor-β1 (TGF-β1)/Smad signaling in thyroid carcinoma cells. However, inhibition of TGF-β1/Smad signaling through silencing TGF-β1 attenuated the promoting effects of KIF2C overexpression on the malignant phenotype of thyroid carcinoma cells. Besides, overexpression of TGF-β1 suppressed the inhibitory effect of KIF2C knockdown on the proliferation and metastasis of thyroid carcinoma cells. In conclusion, our findings demonstrated that KIF2C contributed to the malignant phenotype of thyroid carcinoma cells by inducing the activation of TGF-β1/Smad signaling, thus uncovering a novel mechanism for thyroid carcinoma progression.

M2-like tumor-associated macrophages-secreted Wnt1 and Wnt3a promotes dedifferentiation and metastasis via activating β-catenin pathway in thyroid cancer.

Thyroid carcinoma (TC) has been a global issue for its rapid increasing incidence worldwide. Although most TC was not so aggressive with a good prognosis, treatment against anaplastic TC was relatively limited and the mechanisms are not well elucidated yet. TC cell lines (IHH4 and TPC-1) were used. Flow cytometry was used to identify the surface marker of M2-like tumor-associated macrophages (TAMs) from cell culture. Quantitative real-time polymerase chain reaction, western blot analysis, immunostaining, and immunohistochemistry were used to detect the expression of Wnt1, Wnt3a, components of Wnt/β-catenin pathway, and proliferation/epithelial-mesenchymal transition (EMT)-related proteins. Alkaline phosphatase activity assay, colony formation assay, and transwell assay were used to examine the roles of Wnt1, Wnt3a, and β-catenin pathway in cell dedifferentiation, proliferation, migration, and invasion of TC cells, respectively. Subcutaneous tumor growth was monitored in nude mice. Coculture with M2-like TAMs facilitated dedifferentiation, proliferation, migration, and invasion in TC cells. EMT and proliferation-related proteins were also promoted in cocultured TC cells. The level of Wnt1 and Wnt3a was increased in the coculture system. Block of Wnt1 or Wnt3a suppressed malignant behaviors in cocultured tumor cells. Furthermore, Wnt1 or Wnt3a knockdown inhibited Wnt/β-catenin signaling pathway, and suppressed EMT and proliferation-related signals in cocultured tumor cells. Knockdown of Wnt1 or Wnt3a inhibited tumor growth in xenograft model. M2-like TAMs promoted dedifferentiation, proliferation, and metastasis of TC by Wnt1 and Wnt3a secretion and ensuing β-catenin activation.

Mesenchymal stem cells-originated exosomal microRNA-152 impairs proliferation, invasion and migration of thyroid carcinoma cells by interacting with DPP4.

Thyroid carcinoma (THCA) is the most prevalent tumor in the endocrine system with an increasing incidence. Recent studies have underscored the function of microRNAs (miRNAs) in THCA. Nevertheless, knowledge regarding the effects of exosomal miRNAs in THCA is still limited. This report intended to probe the regulatory effects of exosomal miR-152 on THCA and the underlying mechanism. The expression profile of miR-152 was studied in clinical samples as well as B-CPAP and TPC-1 cells. Transwell, CCK-8, and flow cytometric assays were performed to investigate the roles of miR-152 on invasion, migration, proliferation, and apoptosis in B-CPAP and TPC-1 cells. The putative target of miR-152 was predicted using the bioinformatic analysis, and the targeting relationship was confirmed verified subsequently. Afterward, exosomes were isolated from bone marrow mesenchymal stem cells (BM-MSCs) and co-cultured with B-CPAP and TPC-1 cells to explore the function of exosomal miR-152 on THCA cells. miR-152 was reduced in THCA tissues and cells. Restoration of miR-152 inhibited proliferation, invasion and migration of B-CPAP and TPC-1 cells, but promoted cell apoptosis. Dipeptidyl dipeptidase 4 (DPP4), a target of miR-152, was found to promote THCA cell invasion and migration. miR-152 ferried by BM-MSCs-derived exosomes repressed THCA cell invasion and migration, and pcDNA-DPP4 weakened the repression effect. Exosomal miR-152 inhibited proliferation, migration and invasion of THCA cells by binding with DPP4, which may represent a novel target for the treatment of THCA.

<p>Knockdown of <em>LINC02471</em> Inhibits Papillary Thyroid Carcinoma Cell Invasion and Metastasis by Targeting miR-375</p>

BackgroundLncRNAs play important roles in papillary thyroid carcinoma (PTC). LINC02471 has been reported to be related to PTC prognosis. The current study aimed to investigate the effects of LINC02471 on human PTC cells.MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine LINC02471 expression in PTC tissues and cells and miR-375 expression in PTC cells. SiLINC02471, miR-375 mimic and miR-375 inhibitor were used for cell transfection. Cell proliferation, apoptosis, migration, and invasion were detected by performing Cell Counting Kit-8 (CCK-8), clone formation assay, flow cytometry, scratch assay, and transwell assay. Western blot was carried out to detect protein levels of E-cadherin, N-cadherin and Snail. The target gene for LINC02471 was verified by dual-luciferase reporter assay.ResultsLINC02471 was highly expressed in PTC tissues and cells. After silencing LINC02471, cell proliferation, migration and invasion were reduced, but cell apoptosis was increased. SiLINC02471 increased the expressions of E-cadherin and miR-375, and inhibited the expressions of N-Cadherin and Snail. LINC02471 directly targeted miR-375 in PTC cells. Overexpression of miR-375 inhibited the proliferation, migration, invasion of PTC cells and reduced the expressions of N-Cadherin and Snail but promoted the cell apoptosis and increased E-cadherin expression, while miR-375 inhibitor produced opposite effects to overexpressed miR-375. After inhibiting miR-375 expression, siLINC02471 reversed the effect of miR-375 inhibitor.ConclusionLINC02471 could promote the development of PTC. Knocking down LINC02471 could inhibit invasion and metastasis and promote PTC cell apoptosis through directly targeting miR-375.

MicroRNA‑15b‑5p exerts its tumor repressive role via targeting GDI2: A novel insight into the pathogenesis of thyroid carcinoma.

Thyroid carcinoma (THCA) is a malignant tumor of the endocrine system. Previous studies have revealed the vital roles of microRNAs (miRNAs/miRs) in THCA procession. The present study aimed to explore the effects of miR-15b-5p on the progression of THCA and its targeting mechanism. The data of THCA and healthy samples were firstly collected from starbase2.0 and used to analyze the relationship of miR-15b-5p with THCA. Dual-luciferase assay was performed to detect the direct interaction between miR-15b-5p and the predicted target gene GDP dissociation inhibitor 2 (GDI2). The effects of miR-15b-5p and GDI2 on the overall survival of patients with THCA were analyzed using Kaplan-Meier analysis with log rank test. Cell Counting Kit-8 and Transwell assays were conducted to assess the impacts of miR-15b-5p and GDI2 on the proliferation and invasion of THCA cells. Reverse transcription-quantitative PCR and western blot analyses were performed to analyze the expression levels of the related miRNAs and proteins, respectively. miR-15b-5p was found to be downregulated both in THCA tissues and cells, and the low expression of miR-15b-5p was associated with the short overall survival time of patients. Moreover, the upregulation or downregulation of miR-15b-5p could inhibit or enhance the proliferation and invasion of THCA cells, respectively. miR-15b-5p reduced the protein expression levels of matrix metalloproteinase (MMP)2 and MMP9, which were related to cell invasion. Furthermore, GDI2, which was enhanced in THCA and related to the poor prognosis of patients with THCA, was identified as the target gene of miR-15b-5p and negatively regulated by miR-15b-5p. Additional experiments demonstrated that GDI2 overexpression could significantly reduce the antitumor effect of miR-15b-5p and its inhibitory action on the expression levels of MMP2 and MMP9. Thus, the results indicated a potential tumor suppressive role of miR-15b-5p in THCA, which was mainly exerted by targeting GDI2 and modulating MMP2 and MMP9. These findings will increase the understanding on the pathogenesis of THCA and provide novel candidates for THCA therapy.

OTUD6B-AS1 Inhibits Viability, Migration, and Invasion of Thyroid Carcinoma by Targeting miR-183-5p and miR-21.

Background: The long noncoding RNA (lncRNA) functions as a regulator of initiation, progression, and metastasis of thyroid carcinomas. lncRNA OTUD6B antisense RNA 1 (OTUD6B-AS1) is a tumor-suppressive noncoding RNA in clear cell renal cell carcinoma. The role of OTUD6B-AS1 in thyroid carcinomas has not been reported yet. We aim to investigate the expression and biological functions of OTUD6B-AS1 in thyroid carcinomas.Methods: The expression level of OTUD6B-AS1 was measured in 60 paired human thyroid carcinoma tissues and corresponding adjacent normal thyroid tissues. The correlations between the OTUD6B-AS1 expression levels and clinicopathological features were evaluated using the Mann-Whitney test. The effects of OTUD6B-AS1 on thyroid carcinoma cells were determined via the MTT and transwell assays. The potential targets of OTUD6B-AS1 were screened using the online programs OncomiR and StarBase 3.0, and the LncBase Predicted v.2. Luciferase reporter assay was used to confirm the interactions between OTUD6B-AS1 and its potential targets.Results: OTUD6B-AS1 was downregulated in thyroid carcinoma tissue samples. The expression of OTUD6B-AS1 correlated with tumor size, clinical stage, and lymphatic metastasis of thyroid carcinoma. Overexpression of OTUD6B-AS1 significantly decreased the viability, migration, and invasion of thyroid carcinoma cells. Online programs predicted miR-183-5p and miR-21 as potential targets of OTUD6B-AS1. Luciferase reporter assays showed miR-183-5p and miR-21 bound to OTUD6B-AS1. Moreover, overexpression of miR-183-5p and miR-21 compromised the inhibitory effects of OTUD6B-AS1 on viability, migration, and invasion of thyroid carcinoma cells.Conclusions: Taken together, our findings present in vitro evidence of lncRNA OTUD6B-AS1 as a tumor suppressor in thyroid carcinomas. OTUD6B-AS1 inhibits viability, migration, and invasion of thyroid carcinoma by targeting miR-183-5p and miR-21.

Downregulation of microR-147b represses the proliferation and invasion of thyroid carcinoma cells by inhibiting Wnt/β-catenin signaling via targeting SOX15

microRNA-147b (miR-147b) is a newly identified tumor-related miRNA that is dysregulated in multiple cancer types. Yet, the role of miR-147b in thyroid carcinoma remains unknown. Herein, we found that miR-147b expression was upregulated in thyroid carcinoma tissues and cell lines. miR-147b inhibition decreased the proliferation, colony formation, and invasion of thyroid carcinoma cells. The tumor suppressive gene SRY-related high-mobility-group box gene 15 (SOX15) was predicted as a miR-147b target gene. SOX15 expression was markedly decreased in thyroid carcinoma tissues and inversely correlated with the miR-147b expression. SOX15 overexpression repressed the proliferation and invasion of thyroid carcinoma cells associated with downregulation of Wnt/β-catenin signaling. SOX15 knockdown abolished the miR-147b-inhibition-mediated antitumor effect. miR-147b inhibition or SOX15 overexpression retarded the tumor growth of thyroid carcinoma cells in vivo. Overall, our study suggests that miR-147b inhibition restrains the proliferation and invasion of thyroid carcinoma cells through upregulation of SOX15 and inhibition of Wnt/β-catenin signaling.

Oleanolic acid inhibits cell proliferation migration and invasion and induces SW579 thyroid cancer cell line apoptosis by targeting forkhead transcription factor A.

Oleanolic acid (OA) is a naturally occurring triterpenoid that possesses antitumor activity against several tumor cell lines. However, the potential mechanism underlying OA-induced thyroid carcinoma cell death is poorly understood. We investigated the biological functions of OA by performing migration, invasion, colony formation, and apoptosis assays on SW579 cells. Forkhead box A1 (FOXA1) expression was used to predict poor prognosis in patients with thyroid carcinoma among the TCGA samples from the UALCAN and gene expression profiling interactive analysis databases. Western blot was used to detect protein expression level. Results revealed that OA inhibited the migration, colony formation, and invasion of thyroid carcinoma cells in a dose-dependent manner. Further investigation verified that OA treatment induced significant apoptosis of thyroid carcinoma cells. Moreover, high FOXA1 expression predicted the poor prognosis of patients with thyroid cancer. The proliferation, migration, and invasion of thyroid carcinoma cells were significantly decreased when FOXA1 was silenced. OA significantly increased Akt phosphorylation and reduced FOXA1 expression in SW579 cells, but only PI3K/Akt inhibitor LY294002 attenuated OA-induced FOXA1 downregulation. Furthermore, Akt overexpression suppressed the FOXA1 expression in SW579 cells. In addition, molecular docking assay revealed that OA possessed high affinity toward FOXA1 with a low binding energy. OA may be a potential chemotherapeutic agent against thyroid carcinoma cells.

METTL7B promotes migration and invasion in thyroid cancer through epithelial-mesenchymal transition.

Thyroid cancer is associated with one of the most malignant endocrine tumors. However, molecular mechanisms underlying thyroid tumorigenesis and progression remain unclear. In order to investigate these mechanisms, we performed whole-transcriptome sequencing, which indicated that a differentially expressed gene, METTL7B, was highly expressed in thyroid cancers. We analyzed METTL7B expression using TCGA and performed qRT-PCR on tissue samples. Moreover, an analysis of clinicopathological characteristics revealed a positive correlation between METTL7B and lymph node metastasis. A series of in vitro experiments indicated that METTL7B enhanced migration and invasion of thyroid carcinoma cells. Further studies revealed that METTL7B may enhance TGF-β1-induced epithelial-mesenchymal transition (EMT). Our results indicate that METTL7B may promote metastasis of thyroid cancer through EMT and may therefore be considered as a potential biomarker for the diagnosis and prognosis of thyroid carcinoma.