Thyroid Cancer Progression Research Articles

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.

Gene Analysis of Cancer Stem Cells in Thyroid Cancer

<i>Objective </i>Recurrence and drug resistance in different thyroid cancer in the clinic are associated with tumor stem cells. To investigate the differences in transcript levels of tumor stem cell-associated genes in different thyroid cancer cell lines and their correlation with tumor pathways for identifing factors affecting thyroid cancer progression. <i>Methods </i>Wound healing assay was performed to analyze cell migration; to compare the transcript levels of tumor stem cell related genes CD133, OCT4, ABCG2, ALDH2, Nanog, CD44, CD24, EMT and thyroid specific genes in different thyroid cancer cell lines; to analyze the correlation between the above genes and tumor pathways and the correlation between genes using R software GSVA package combined with TCGA database. <i>Results</i> Wound healing results showed that thyroid cancer cell lines TPC-1 and ATC healed faster than normal cells. qPCR showed significantly different expression of EGFR, CD44, CD24 and ABCG2 in ATC and TPC-1 compared to Nthy-ori 3-1. EGFR and ABCG2 were highly expressed in ATC cell lines, while CD24 gene was highly expressed in TPC -1; TTF2 was significantly low expressed in both ATC and TPC-1 cell lines. Correlation analysis showed that ABCG2 and OCT4 were negatively correlated with inflammatory response, ALDH2 with P53 signaling pathway, CD24 with ECM degradation and P53 signaling pathway, Nanog with MYC target gene pathway, and CD44 with reactive oxygen species (ROS) gene upregulation in thyroid cancer; EGFR was positively correlated with TGFB signaling pathway. The genes ALDH2, ABCG2 and CD44 were significantly and positively correlated with TPO and TG. <i>Conclusion </i>The transcriptional levels of tumor stem cell genes differed greatly among different types of thyroid cancer and were significantly associated with tumor signaling pathways. It may be related to signaling pathways that exacerbate the development of thyroid cancer.

CircNDST1 promotes papillary thyroid cancer progression via its interaction with CSNK2A1 to activate the PI3K–Akt pathway and epithelial–mesenchymal transition

BackgroundMultiple studies have established a strong relationship between circRNA and cancer progression. Cervical lymph node metastasis is a key factor influencing the surgical approach and distant metastasis of papillary thyroid cancer (PTC). However, the role of circNDST1 in PTC has not been investigated. Our research focused on revealing the function and mechanism of action of circNDST1 in PTC.MethodsHigh-throughput sequencing and qPCR were used to assess the expression of circRNA in PTC tissues with extensive cervical lymph node metastasis and circNDST1 in cell lines, respectively. The proliferative effects of circNDST1 in vitro and in vivo were analyzed using CCK8, clone formation assay, EdU, and nude mouse tumorigenesis assay. The transwell scratch assay was employed in the scrutiny of the effect of circNDST1 on the migration and invasion abilities of thyroid cancer cells, while circNDST1’s influence on the PI3K–Akt pathway and the Epithelial–Mesenchymal Transition (EMT) key protein expression was evaluated utilizing RNA sequencing and western blot. RNA pull-down and RIP were used to examine the binding of circNDST1 to CSNK2A1.ResultsCircNDST1 was highly expressed in PTC cell lines, but knocking it down inhibited the proliferation, migration, and invasive abilities of TPC1 and KTC1 cell lines. CircNDST1 bonded with CSNK2A1 and promoted the interaction between CSNK2A1 and Akt, leading to the activation of the PI3K–Akt pathway and EMT.ConclusionCircNDST1’s high expression boosted thyroid cancer progression through the activation of the PI3K–Akt pathway and EMT in a CSNK2A1-dependent manner

LINC01089 blocks malignant progression of thyroid cancer by binding miR-27b-3p to enhance the FBLN5 protein level

LINC01089 suppresses the malignant progression of breast, colorectal, and non-small cell lung cancers. However, the function of LINC01089 in thyroid cancer has not yet been elucidated. Here, The Cancer Genome Atlas (TCGA) database showed that LINC01089 expression is remarkably reduced in thyroid cancer tissues. Lower LINC01089 expression was correlated with higher tumor stage and regional lymph node metastasis. Furthermore, LINC01089 overexpression effectively blocked thyroid cancer cell proliferation, migration, and invasion. LINC01089 acted as a competing endogenous RNA for miR-27b-3p, thus inhibiting miR-27b-3p expression. miR-27b-3p overexpression promoted the proliferation, migration, and invasion of thyroid cancer, reversing the effect of LINC01089 overexpression on thyroid cancer. Fibulin-5 (FBLN5) was discovered as a target of miR-27b-3p in thyroid cancer. FBLN5 expression was found to be underexpressed in thyroid cancer and was enhanced and reduced by LINC00987 overexpression and miR-27b-3p overexpression, respectively. Furthermore, FBLN5 knockdown promoted the malignant progression of thyroid cancer cells by counteracting the effect of LINC00987. In conclusion, LINC01089 plays a tumor-suppressive role by binding miR-27b-3p to increase FBLN5 expression, confirming that LINC01089 has tremendous potential to become a therapeutic target for thyroid cancer treatment.

Role of Sostdc1 in skeletal biology and cancer.

Sclerostin domain-containing protein-1 (Sostdc1) is a member of the sclerostin family and encodes a secreted 28-32kDa protein with a cystine knot-like domain and two N-linked glycosylation sites. Sostdc1 functions as an antagonist to bone morphogenetic protein (BMP), mediating BMP signaling. It also interacts with LRP6, mediating LRP6 and Wnt signaling, thus regulating cellular proliferation, differentiation, and programmed cell death. Sostdc1 plays various roles in the skin, intestines, brain, lungs, kidneys, and vasculature. Deletion of Sostdc1 gene in mice resulted in supernumerary teeth and improved the loss of renal function in Alport syndrome. In the skeletal system, Sostdc1 is essential for bone metabolism, bone density maintenance, and fracture healing. Recently, Sostdc1 has been found to be closely related to the development and progression of multiple cancer types, including breast, renal, gastric, and thyroid cancers. This article summarises the role of Sostdc1 in skeletal biology and related cancers to provide a theoretical basis for the treatment of related diseases.

Pyruvate carboxylase promotes malignant transformation of papillary thyroid carcinoma and reduces iodine uptake

Previous studies have shown that pyruvate carboxylase (PC) plays a key role in the occurrence and progression of thyroid cancer (TC); however, the relationship between PC and iodine-refractory TC is unclear. Therefore, the present study aimed to investigate the molecular mechanism of PC in the malignant progression and loss of iodine uptake in papillary TC (PTC) and to explore the potential therapeutic effect of PC inhibitors in iodine-refractory PTC. PC increased cell proliferation, invasion, and metastasis, inhibited expression of the iodine metabolism-related genes TSHR, NIS, TPO, and TG, and decreased the iodine-uptake capacity by activating the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway in PTC cell lines. Furthermore, the PC inhibitor ZY-444 effectively inhibited the activation of PC, reduced the malignant invasiveness, and restored the expression of iodine metabolism-related genes and the iodine-uptake capacity in PTC cells. These findings suggest that PC activation is involved in the progression of iodine-refractory TC and that PC inhibitors may represent a potentially novel targeted therapy for iodine-refractory TC.

A Review and In Silico Analysis of Tissue and Exosomal Circular RNAs: Opportunities and Challenges in Thyroid Cancer.

Simple SummaryThyroid cancer is the most common endocrine neoplasm. Recently, knowledge of the molecular genetic changes of thyroid cancer has dramatically improved. Understanding the roles of these molecular changes in thyroid cancer tumorigenesis and progression is essential in developing a successful treatment strategy and improving disease outcomes. As a family of non-coding RNAs, circular RNAs (circRNAs) have been involved in several aspects of the physiological and pathological processes of the cells. The roles of circRNAs in cancer development and progress are evident. In the current review, we aimed to explore the clinical potential of circRNAs as potential diagnostic, prognostic, and therapeutic targets in thyroid cancer. Furthermore, screening the genome-wide circRNAs and performing functional enrichment analyses for all associated dysregulated circRNAs in thyroid cancer have been done. Given the unique advantages circRNAs have, such as superior stability, higher abundance, and presence in different body fluids, this family of non-coding RNAs could be promising diagnostic and prognostic biomarkers and potential therapeutic targets for thyroid cancer.Thyroid cancer (TC) is the most common endocrine tumor. The genetic and epigenetic molecular alterations of TC have become more evident in recent years. However, a deeper understanding of the roles these molecular changes play in TC tumorigenesis and progression is essential in developing a successful treatment strategy and improving patients’ prognoses. Circular RNAs (circRNAs), a family of non-coding RNAs, have been implicated in several aspects of carcinogenesis in multiple cancers, including TC. In the current review, we aimed to explore the clinical potential of circRNAs as putative diagnostic, prognostic, and therapeutic targets in TC. The current analyses, including genome-wide circRNA screening and functional enrichment for all deregulated circRNA expression signatures, show that circRNAs display atypical contributions, such as sponging for microRNAs, regulating transcription and translation processes, and decoying for proteins. Given their exceptional clinical advantages, such as higher stability, wider abundance, and occurrence in several body fluids, circRNAs are promising prognostic and theranostic biomarkers for TC.

Traces of JC polyomavirus in papillary thyroid cancer: a comprehensive study in Iran.

BackgroundJC polyomavirus (JCPyV) is known to induce solid tumors such as astrocytomas, glioblastomas, and neuroblastomas in experimental animals, and recent studies have shown that the virus may be correlated with carcinogenesis. This study aimed to evaluate the impact of JCPyV on the progression of papillary thyroid cancer (PTC).MethodsA total of 1057 samples, including 645 paraffin-embedded PTC biopsy samples (PEBS) and 412 fresh biopsy samples (FBS), and 1057 adjacent non-cancerous samples were evaluated for the presence of JCPyV DNA and RNA.ResultsWe observed that 10.8% (114/1057) samples, including 17.5% (72/412) FBS and 6.5% (42/645) PEBS were positive for the JCPyV DNA. Among the JCPyV-positive samples, the mean JCPyV copy number was lower in patients with PEBS (0.3 × 10–4 ± 0.1 × 10–4 copies/cell) compared to FBS (1.8 × 10–1 ± 0.4 × 10–1 copies/cell) and non-PTC normal samples (0.2 × 10–5 ± 0.01 × 10–5 copies/cell), with a statistically significant difference (P < 0.001). The LT-Ag RNA expression was lower in PEBS than in FBS, while no VP1 gene transcript expression was found.ConclusionsAlthough our results confirmed the presence of JCPyV in some Iranian patients with PTC, more research is needed to verify these results.

Survival-based bioinformatics analysis to identify hub long non-coding RNAs along with lncRNA-miRNA-mRNA network for potential diagnosis/prognosis of thyroid cancer.

Thyroid cancer (TC) is the most common endocrine cancer, accounting for 1.7% of all cancer cases. It has been reported that the existing approach to diagnosing TC is problematic. Therefore, it is essential to develop molecular biomarkers to improve the accuracy of the diagnosis. This study aimed to screen hub lncRNAs in the ceRNA network (ceRNET) connected to TC formation and progression based on the overall survival rate. In this study, first, RNA-seq data from the GDC database were collected. A package called edgeR in R programming language was then used to obtain differentially expressed lncRNAs (DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) in TC patients' samples compared to normal samples. Second, DEmRNAs were analyzed for their functional enrichment. Third, to identify RNAs associated with overall survival, the overall survival of these RNAs was analyzed using the Kaplan-Meier plotter database to create a survival associated with the ceRNA network (survival-related ceRNET). Next, the GeneMANIA plugin was used to construct a PPI network to better understand survival-related DEmRNA interactions. The survival ceRNET was then visualized with the Cytoscape software, and hub genes, including hub lncRNAs and hub mRNAs, were identified using the CytoHubba plugin. We found 45 DElncRNAs, 28 DEmiRNAs, and 723 DEmRNAs among thyroid tumor tissue and non-tumor tissue samples. According to KEGG, GO and DO analyses, 723 DEmRNAs were mainly enriched in cancer-related pathways. Importantly, the results found that ten DElncRNAs, four DEmiRNAs, and 68 DEmRNAs are associated with overall survival. In this account, the PPI network was constructed for 68 survival-related DEmRNAs, and ADAMTS9, DTX4, and CLDN10 were identified as hub genes. The ceRNET was created by combining six lncRNAs, 109 miRNAs, and 22 mRNAs related to survival using Cytoscape. in this network, ten hub RNAs were identified by the CytoHubba plugin, including mRNAs (CTXND1, XKRX, IGFBP2, ENTPD1, GALNT7, ADAMTS9) and lncRNAs (AC090673.1, AL162511.1, LINC02454, AL365259.1). This study suggests that three lncRNAs, including AL162511.1, AC090673.1, and AL365259.1, could be reliable diagnostic biomarkers for TC. The findings of this study provide a basis for future studies on the therapeutic potential of these lncRNAs.

ZCCHC12 promotes the progression of osteosarcoma via PI3K/AKT pathway.

Researchers have reported that zinc finger CCHC domain containing 12 gene (ZCCHC12) plays a role in the progression and tumorigenesis of papillary thyroid cancer. However, the biological role of ZCCHC12 in osteosarcoma (OS) remains unknown. ZCCHC12 was highly upregulated in OS cell lines according to our present study. Also, our subsequent assays demonstrated that ZCCHC12 enhanced the proliferation, tumor growth and migration of OS cells. Moreover, the epithelial-mesenchymal transition (EMT) of OS cells was also promoted by ZCCHC12. In addition, downregulation of ZCCHC12 induced apoptosis and S-phase arrest in OS cells. Then, our study indicated that ZCCHC12 exerts its oncogenic function in OS cells by activating the PI3K/AKT pathway. Inhibition of the PI3K/AKT pathway greatly limits the oncogenic function of ZCCHC12 in OS cells. Also, overexpression of ZCCHC12 promotes tumor growth in vivo. Altogether, our study suggests ZCCHC12 promotes OS cells progression by activating the PI3K/AKT pathway. The ZCCHC12 gene may be a novel diagnostic and therapeutic target for OS.

Adrenomedullin2 stimulates progression of thyroid cancer in mice and humans under nutrient excess conditions.

Thyroid cancer is associated with genetic alterations, e.g. BRAFV600E , which may cause carcinomatous changes in hormone-secreting epithelial cells. Epidemiological studies have shown that overnutrition is related to the development and progression of cancer. In this study, we attempted to identify the cell nonautonomous factor responsible for the progression of BRAFV600E thyroid cancer under overnutrition conditions. We developed a mouse model for inducible thyrocyte-specific activation of BRAFV600E , which showed features similar to those of human papillary thyroid cancer. LSL-BrafV600E ;TgCreERT2 showed thyroid tumour development in the entire thyroid, and the tumour showed more abnormal cellular features with mitochondrial abnormalities in mice fed a high-fat diet (HFD). Transcriptomics revealed that adrenomedullin2 (Adm2) was increased in LSL-BrafV600E ;TgCreERT2 mice fed HFD. ADM2 was upregulated on the addition of a mitochondrial complex I inhibitor or palmitic acid with integrated stress response (ISR) in cancer cells. ADM2 stimulated protein kinase A and extracellular signal-regulated kinase in vitro. The knockdown of ADM2 suppressed the proliferation and migration of thyroid cancer cells. We searched The Cancer Genome Atlas and Genotype-Tissue Expression databases and found that increased ADM2 expression was associated with ISR and poor overall survival. Consistently, upregulated ADM2 expression in tumour cells and circulating ADM2 molecules were associated with aggressive clinicopathological parameters, including body mass index, in thyroid cancer patients. Collectively, we identified that ADM2 is released from cancer cells under mitochondrial stress resulting from overnutrition and acts as a secretory factor determining the progressive properties of thyroid cancer. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Erratum to “A two-microRNA signature predicts the progression of male thyroid cancer”

[This corrects the article DOI: 10.1515/biol-2021-0099.].

ALKBH5 inhibits thyroid cancer progression by promoting ferroptosis through TIAM1-Nrf2/HO-1 axis.

As a critical catalytic subunit of N6-methyladenosine (m6A) modification in messenger RNA, ALKBH5 has been reported to affect the progression of numerous tumors. However, the functions and mechanisms of ALKBH5 in thyroid cancer remain largely unknown. Relative mRNA and protein levels in thyroid cancer tissues and cells were detected by qRT-PCR and western blot, respectively. The proliferation and viability were evaluated using colony formation and CCK-8 assays. Intracellular ironlevel was measured by an iron colorimetric assay kit. ROS level was determined using CellRox Green reagent. TIAM1 mRNA m6A level was detected by MeRIP. Xenograft tumor growth was performed to examine the role of ALKBH5 in thyroid tumor growth in vivo. ALKBH5 was decreased in thyroid cancer tissues and cells. ALKBH5 overexpression inhibited thyroid cancer cell proliferation and increased the levels of Fe2+ and ROS and reduced the proteins expression of GPX4 and SLC7A11. Furthermore, overexpression of ALKBH5 inhibited TIAM1 expression by m6A modification, and overexpression of TIAM1 reversed the regulatory of oe-ALKBH5 on cell proliferation and ferroptosis in thyroid cancer. In addition, TIAM1 was elevated in thyroid cancer, and TIAM1 knockdown repressed thyroid cancer cell proliferation and promoted ferroptosis through regulating Nrf2/HO-1 axis. In addition, in vivo evidences also showed that ALKBH5 suppressed thyroid cancer progression by decreasing the m6A level of TIAM1. Our findings suggested that ALKBH5 inhibited thyroid cancer progression by inducing ferroptosis through m6A-TIAM1-Nrf2/HO-1 axis, suggesting ALKBH5 might be a potential target molecule for the treatment and diagnosis of thyroid cancer.

Inhibiting ERK dimerization ameliorates BRAF-driven anaplastic thyroid cancer

BackgroundRAS-to-ERK signaling is crucial for the onset and progression of advanced thyroid carcinoma, and blocking ERK dimerization provides a therapeutic benefit in several human carcinomas. Here we analyzed the effects of DEL-22379, a relatively specific ERK dimerization inhibitor, on the activation of the RAS-to-ERK signaling cascade and on tumor-related processes in vitro and in vivo.MethodsWe used a panel of four human anaplastic thyroid carcinoma (ATC) cell lines harboring BRAF or RAS mutations to analyze ERK dynamics and tumor-specific characteristics. We also assessed the impact of DEL-22379 on the transcriptional landscape of ATC cell lines using RNA-sequencing and evaluated its therapeutic efficacy in an orthotopic mouse model of ATC.ResultsDEL-22379 impaired upstream ERK activation in BRAF- but not RAS-mutant cells. Cell viability and metastasis-related processes were attenuated by DEL-22379 treatment, but mostly in BRAF-mutant cells, whereas in vivo tumor growth and dissemination were strongly reduced for BRAF-mutant cells and mildly reduced for RAS-mutant cells. Transcriptomics analyses indicated that DEL-22379 modulated the transcriptional landscape of BRAF- and RAS-mutant cells in opposite directions.ConclusionsOur findings establish that BRAF- and RAS-mutant thyroid cells respond differentially to DEL-22379, which cannot be explained by the previously described mechanism of action of the inhibitor. Nonetheless, DEL-22379 demonstrated significant anti-tumor effects against BRAF-mutant cells in vivo with an apparent lack of toxicity, making it an interesting candidate for the development of combinatorial treatments. Our data underscore the differences elicited by the specific driver mutation for thyroid cancer onset and progression, which should be considered for experimental and clinical approaches.

Thyroid Cancer and Fibroblasts.

Simple SummaryThyroid cancer is the most common solid tumor of the endocrine glands. The cancer cell contribution to thyroid cancer development and progression has been studied extensively, whereas the involvement of the tumor microenvironment, particularly of cancer-associated fibroblasts (CAFs), in thyroid cancer growth still must be largely analyzed. The tumor microenvironment, comprising molecules, blood and lymphatic tumor vessels and several non cancer stromal cells, such as CAFs, dramatically influences solid tumor growth and therapy resistance. In particular, investigations on CAF contribution to solid tumor growth and therapeutic resistance represent an important area of oncological research. Moreover, studies focused on the role of CAFs in thyroid cancer could lead to a better comprehension of mechanisms regulating cancer growth and to the development of new therapeutic strategies. Therefore, in this paper, we review the hallmarks of CAFs and their role on thyroid cancer.Thyroid cancer is the most common type of endocrine cancer, and its prevalence continue to rise. Non-metastatic thyroid cancer patients are successfully treated. However, looking for new therapeutic strategies is of great importance for metastatic thyroid cancers that still lead to death. With respect to this, the tumor microenvironment (TME), which plays a key role in tumor progression, should be considered as a new promising therapeutic target to hamper thyroid cancer progression. Indeed, thyroid tumors consist of cancer cells and a heterogeneous and ever-changing niche, represented by the TME, which contributes to establishing most of the features of cancer cells. The TME consists of extracellular matrix (ECM) molecules, soluble factors, metabolites, blood and lymphatic tumor vessels and several stromal cell types that, by interacting with each other and with tumor cells, affect TME remodeling, cancer growth and progression. Among the thyroid TME components, cancer-associated fibroblasts (CAFs) have gained more attention in the last years. Indeed, recent important evidence showed that thyroid CAFs strongly sustain thyroid cancer growth and progression by producing soluble factors and ECM proteins, which, in turn, deeply affect thyroid cancer cell behavior and aggressiveness. Hence, in this article, we describe the thyroid TME, focusing on the desmoplastic stromal reaction, which is a powerful indicator of thyroid cancer progression and an invasive growth pattern. In addition, we discuss the origins and features of the thyroid CAFs, their influence on thyroid cancer growth and progression, their role in remodeling the ECM and their immune-modulating functions. We finally debate therapeutic perspectives targeting CAFs.

Circular RNA PVT1 promotes progression of thyroid cancer by competitively binding miR-384.

Plasmacytoma variant translocation 1 circular RNA (circPVT1) is involved in the initiation and development of several types of cancer. However, the underlying molecular role of circPVT1 in tumorigenesis of thyroid cancer remains to be elucidated. In the present study, relative expression of circPVT1 was markedly upregulated in thyroid cancer compared with adjacent normal tissue. circPVT1 expression was associated with clinical stage and lymph node metastasis. Furthermore, Cell Counting Kit-8, colony formation and Transwell chamber assays demonstrated that knockdown of circPVT1 decreased proliferation, migration and invasion of thyroid cancer cells in vitro. Moreover, circPVT1 directly interacted with microRNA (miR)-384, as shown by bioinformatics prediction and dual luciferase and RNA pull-down assay. miR-384 inhibition partially reversed the circPVT1 knockdown-mediated inhibitory effect on proliferation, migration and invasion of thyroid cancer cells. In summary, these findings demonstrated that circPVT1 may be a potential therapeutic target for thyroid cancer.

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.

Assessment of Preoperative TSH Serum Level and Thyroid Cancer Occurrence in Patients with AUS/FLUS Thyroid Nodule Diagnosis.

Thyroid-stimulating hormone (TSH) is a growth factor associated with the initiation and progression of well-differentiated thyroid cancer (WDTC). Atypia of undetermined significance and follicular lesion of undetermined significance (AUS/FLUS) are the most uncertain cytological diagnoses of thyroid nodules. The aim of the study was to determine the association of histopathological diagnosis with preoperative serum TSH levels in patients with AUS/FLUS thyroid nodule diagnosis. Among 5028 individuals with thyroid nodules, 342 (6.8%) with AUS/FLUS diagnoses were analyzed. The frequency of all histopathology diagnoses was assessed for associations with preoperative serum TSH levels. The median TSH concentration was significantly higher in patients with AUS/FLUS diagnosis and histopathology of WDTC than in patients with the same cytology result and histopathology of a benign tumor (p < 0.0001). The diagnostic potential of serum TSH level was determined to evaluate risk of malignancy in patients with thyroid nodules classified into the Bethesda III category. ROC analysis showed the TSH concentration at a cutoff point of 2.5 mIU/L to be an acceptable prognostic factor for WDTC. For this optimal cutoff point, the AUC was 0.877, the sensitivity was 0.830, and the specificity was 0.902. Preoperative serum TSH levels in patients with AUS/FLUS thyroid tumor diagnosis should be taken into consideration in the decision-making process and clinical management.

SPTBN2 Promotes the Progression of Thyroid Cancer by Accelerating G1/S Transition and Inhibiting Apoptosis.

Background Thyroid carcinoma (TC) is an increasingly common malignancy of endocrine organs, and its most frequently encountered histotype is papillary thyroid cancer (PTC). Identifying new potential gene alterations is important for completely elucidating the mechanism of PTC initiation and progression. Thus, we performed whole transcriptome sequence analysis (RNA-seq) on 79 PTC tissue samples and paired adjacent nontumor tissue samples to study the molecular mechanism of TC tumorigenesis and progression further. The results of RNA-seq analysis showed that spectrin beta, nonerythrocytic 2 (SPTBN2), was markedly overexpressed in PTC tissues relative to that in the paired nontumor tissues. Additionally, the analysis results for 502 PTC samples and 58 nontumor thyroid samples from The Cancer Genome Atlas dataset were consistent with our RNA-seq results. However, the molecular mechanisms and function of SPTBN2 in TC progression remain unknown. Methods We examined SPTBN2 gene expression in 48 papillary thyroid tumor tissues and paired adjacent normal thyroid tissues by using qRT-PCR. SPTBN2 expression in the TC cell lines was silenced by small interfering RNA. Then, the transfected TC cells were used to investigate the in vitro function of SPTBN2. Result The expression of SPTBN2 was significantly upregulated in our RNA-seq cohort, our local validated cohort, and TCGA RNA-seq cohort. The results of the in vitro experiment revealed that in TC cell lines, SPTBN2 downregulation considerably suppressed tumor cell proliferation, the cell cycle, migration, colony formation, and invasion and induced cell apoptosis. Furthermore, the protein levels of CCNE2, CDK2, CDK4, and Bcl-2 were downregulated, and those of P21, Bax, cleaved caspase-8, and cleaved caspase-3 had increased in transfected TC cells relative to in control TC cells. Conclusion The downregulation of SPTBN2 caused apoptosis and retarded G1/S cell cycle transition in TC cells. Thus, SPTBN2 may be a good candidate gene for TC diagnosis and therapy.

Circ_0000144 acts as a miR-1178-3p decoy to promote cell malignancy and angiogenesis by increasing YWHAH expression in papillary thyroid cancer

Papillary thyroid cancer (PTC) is the most common subtype of thyroid cancer. Circular RNA hsa_circ_0000144 (circ_0000144) is related to the progression of thyroid cancer. However, the mechanism by which circ_0000144 accelerates PTC progression is still unclear. Circ_0000144 and YWHAH were upregulated in PTC tissues and cells, while miR-1178-3p had an opposite result. Circ_0000144 silencing constrained PTC cell growth in vitro and in vivo and induced apoptosis and repressed migration, invasion, and angiogenesis of PTC cells in vitro. Circ_0000144 acted as a molecular sponge for miR-1178-3p, which targeted YWHAH. MiR-1178-3p inhibitor reversed circ_0000144 silencing-mediated influence on PTC cell malignancy and angiogenesis. Furthermore, YWHAH overexpression overturned miR-1178-3p mimic-mediated influence on malignant behaviors and angiogenesis of PTC cells. Notably, circ_0000144 regulated YWHAH expression by adsorbing miR-1178-3p. Circ_0000144 promoted cell malignancy and angiogenesis by regulating the miR-1178-3p/YWHAH axis in PTC, offering a novel mechanism for the malignancy and angiogenesis of PTC cells.Graphical