Exosomal circular RNA hsa_circ_007293 promotes proliferation, migration, invasion, and epithelial-mesenchymal transition of papillary thyroid carcinoma cells through regulation of the microRNA-653-5p/paired box 6 axis.

Circular RNAs (circRNAs) or exosomes have been reported to exert key regulatory and/or communication functions in human cancer. Nevertheless, current literature on the effects of exosomal circRNAs on tumor invasion and metastasis in thyroid cancer is incomplete. The role of tumor-derived exosomes in driving in vitro papillary thyroid carcinoma (PTC) progression and metastasis requires further investigation. In our study, Exosomes were harvested from PTC patient serum and PTC cell culture medium. Gene expression analysis in PTC cell lines and exosomes was performed with quantitative reverse-transcription polymerase chain reaction. Transwell, wound healing, Western blot assays, and the cell counting kit-8 were applied for functional analysis. Dual-luciferase reporter assay was used to examine the interaction between hsa_circ_007293 (circ007293), microRNA (miR)-653-5p, and paired box 6 (PAX6). Results showed that circ007293 was enriched in exosomes derived from PTC patient serum and cell culture media. Moreover, circ007293 could enter PTC cells through exosomes, and exosomal circ007293 promoted PTC cell epithelial-mesenchymal transition, invasion, migration, and proliferation. circ007293 knockdown reversed the malignant phenotype of PTC cells in vitro. Additionally, circ007293 could competitively bind with miR-653-5p to regulate PAX6 expression. Notably, miR-653-5p overexpression or PAX6 inhibition suppressed the malignant effects of exosomal circ007293. These results evidenced that exosomal circ007293 induced EMT and augmented the invasive and migratory abilities of PTC cells via the miR-653-5p/PAX6 axis, suggesting that it may serve as a promising biomarker for cancer progression.

Activation of the TGF-ß1/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-ß1 (TGF-ß1)/Smad signaling in thyroid carcinoma cells. However, inhibition of TGF-ß1/Smad signaling through silencing TGF-ß1 attenuated the promoting effects of KIF2C overexpression on the malignant phenotype of thyroid carcinoma cells. Besides, overexpression of TGF-ß1 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-ß1/Smad signaling, thus uncovering a novel mechanism for thyroid carcinoma progression.

Application of Pet-CT Fusion Deep Learning Imaging in Precise Radiotherapy of Thyroid Cancer.

This article explores the value of wall F-FDG PET/Cr imaging in the diagnosis of thyroid cancer, studies its ability to distinguish benign and malignant thyroid lesions, and seeks ways to improve the accuracy of diagnosis. The normal control group selected 40 patients who came to our center for physical examination. In the normal control group, the average value of the standard uptake value of both sides of the thyroid was used as the SUV of the thyroid gland and the highest SUV value of the patient's lesion (SUV max) represented the SUV of the lesion. After injection of imaging agent 18F-FD1G, routine imaging was performed at 1h, time-lapse imaging was performed at 2.5 h, and the changes with conventional imaging were compared to infer the benign and malignant lesions. We used SPSS software to carry out statistical analysis, respectively, carrying out analysis of variance, paired t-test, independent sample t-test, and linear correlation analysis. In the thyroid cancer group, 87.5% of the delayed imaging SUV was higher than the conventional imaging SUV, while 83.33% of the benign disease group had a lower SUV than the conventional imaging SUV. 18F-FDG PET/CT imaging has higher sensitivity and specificity for the diagnosis of recurrence or metastasis in patients with Tg positive. However, it has lower sensitivity and specificity for the diagnosis of 131I-Dx-WBS negative DTC and 18F-FDG PET/CT. The specificity increases with the increase of serum Tg level. The above results confirm that 18F-FDG PET/CT imaging is of great significance for the diagnosis of recurrence or metastasis in patients; with PET/CT imaging, the results changed 16.13% of the Tg-positive and 131I-Dx-WBS negative DTC patients' later treatment decision. The decision-making and curative effect evaluation have certain value.

Silencing of AHNAK2 restricts thyroid carcinoma progression by inhibiting the Wnt/ß-catenin pathway.

AHNAK nucleoprotein 2 (AHNAK2) has been proposed to have an oncogenic role in various human cancers. However, the functional role of AHNAK2 in thyroid carcinoma (TC) progression has never been explored. In this study, quantitative real-time polymerase chain reaction and western blot were conducted to evaluate the expression of genes. The functional role of AHNAK2 was elucidated by cell count kit-8, colony-forming assay, wound-healing assay, and Transwell invasion assay. We found that AHNAK2 was highly expressed in thyroid carcinoma, and it was tightly correlated with the pathological stage in TC. The mRNA and protein levels of AHNAK2 were increased in TC cells. Silencing of AHNAK2 restricted the proliferation, metastasis, and epithelial-mesenchymal transition (EMT) of TC cells. AHNAK2 silencing inhibited the protein expression of ß-catenin and cyclin D1, and AHNAK2 overexpression had the opposite effects. Moreover, LiCl or ICG-001 exposure counteracted the effects of AHNAK2 silencing or upregulation on malignant phenotypes of TC cells. In conclusion, the knockdown of AHNAK2 restrained the proliferation, metastasis, and EMT of TC cells by inhibiting the Wnt/ß-catenin pathway, providing a new potential mechanism of AHNAK2 in understanding the oncogenesis and progression of TC.

LncRNA PVT1 Acts as a Tumor Promoter in Thyroid Cancer and Promotes Tumor Progression by Mediating miR-423-5p-PAK3.

INTRODUCTION: Thyroid cancer (TC) is an endocrine tumor whose risk of onset has been rising, so the deep understanding of its molecular mechanism helps formulate new treatment strategies. METHODS: This paper was aimed at exploring the regulatory mechanism of long non-coding RNA (LncRNA) plasmacytoma variant translocation 1 (PVT1) in TC. The expression of PVT1, miR-423-5p and p21-activated kinase 3 (PAK3) in TC tissues and cell lines was detected by real-time PCR. PAK3 levels were detected by Western blot. Regulatory relationships between target genes and the proliferation, invasion and apoptosis of cells and genes were analyzed. RESULTS: PVT1 and PAK3 upregulated while miR-423-5p downregulated in the tissues and cell lines. PVT1 downregulation inhibited TC cells from malignantly proliferating and invading, and promoted their apoptosis. PVT1 specifically regulated miR-423-5p, and its overexpression could weaken the anti-tumor effect of this miR on TC cells. In addition, miR-423-5p directly targeted PAK3, and knocking down its expression could weaken the inhibitory effect of PAK3 downregulation on TC progression. Besides, PVT1 acted as a competitive endogenous RNA to sponge this miR and thus regulate PAK3 expression. DISCUSSION: In conclusion, PVT1 can mediate the molecular mechanism of the miR-423-5p-PAK3 axis regulatory network on regulating TC, so it is a new direction of treating the disease.