Project description:Papillary thyroid cancer (PTC) is a common endocrine tumor with rapidly increasing incidence in recent years. Although the majority of PTC are relatively indolen and have a good prognosis, it still has a certain proportion of PTC which is highly aggressive with lymphatic metastasis, iodine resistance and easy to recur. Circular RNAs as an class of noncoding RNAs are linked to a variety of tumor processes including PTC. In the current study, a circRNA deep sequencing was performed to identify alterations in circRNA expression levels of PTC tissues. CircTIAM1 was then selected as its increased expression in PTC and associated with migration, apoptosis and proliferation of PTC in vivo and in vitro. Mechanistically, circTIAM1 acted as a sponge of miR-646 and functioned in PTC through targeting mir-646 and HNRNPA1. Fluorescence in situ hybridization (FISH) and luciferase reporter assays further confirmed these connerctions. Overall, our results reveal an important oncogenic role of circTIAM1 in PTC and provide a potentially effective therapeutic strategy for PTC progression.
Project description:To obtain a PTC cell model, primary human thyrocytes have been infected with a retrovirus expressing RET/PTC1 oncogene, using parental thyrocytes as control. The obtained RET/PTC-dependent differential miRNA expression profile, representing the effects of RET/PTC1 oncogene present in about one third of papillary thyroid carcinoma (PTC), models the early event of thyrocytes transformation ending to PTC.
Project description:CircRNA deregulation could be a crucial event in thyroid carcinoma. To investigate circRNA signatures present in several papillary thyroid carcinoma (PTC) patients to complement our understanding of PTC pathogenesis. Using microarray technology, we screened the circRNA profiles in 3 pairs of PTC tumors and matching adjacent normal tissues. This study evaluated circRNAs expression profiles and their ability to serve as reliable biomarkers and new potential diagnostic and therapeutic targets for PTC
Project description:Background: Non-coding circular RNAs (circRNAs) have displayed dysregulated expression in several human cancers. Here, we profiled the circRNA expression of papillary thyroid carcinoma (PTC) tumors to improve our understanding of PTC pathogenesis as well as to identify potential circRNA biomarkers for PTC.
Project description:Well-differentiated tumours (WDT) of the thyroid gland can be difficult to diagnose. Focal nuclear clearing can be suggestive of a papillary thyroid carcinoma (PTC), while questionable vascular or capsular penetration may raise the possibility of diagnosis of a follicular thyroid carcinoma (FTC). The recently proposed term “thyroid tumours of uncertain malignant potential” (TT-UMP) defines cases showing inconclusive morphological evidence of malignancy. We use microRNA (miRNA) expression profiling to analyze 42 well differentiated thyroid tumours including 7 follicular tumours of uncertain malignant potential (FT-UMP), 6 well differentiated tumours of uncertain malignant potential (WDT-UMP), 7 follicular thyroid adenomas (FTA), 5 follicular variant of papillary thyroid carcinoma (FV-PTC) 6 follicular thyroid carcinoma (FTC), and 11 conventional papillary thyroid carcinoma (C-PTC) with 6 C-PTC mutated for BRAFV600E (C-PTC-mut) and 5 not mutated: wild type (C-PTC-wt). Comparison of these 13 tumours of uncertain malignant potential (7 FT-UMP and 6 WDT-UMP) with those obtained from 16 PTC (11 C-PTC and 5 FV-PTC), 6 FTC and 7 FTA is performed in order to clarify the relationships between TT-UMP and the morphologically well characterized categories of thyroid tumours (i.e. C-PTC, FV-PTC, FTC and FTA). In first, each pathological sample (“L” for Lesional tissue) is compared with its matched control (“S” for Safe tissue) for the 42 patients (84 miRNA microarray slides). This control was taken from the same patient at a large distance from the tumour. Secondly, the perilesional tissue from the same patients but 2 (1 PTC and 1 adenoma, without enough RNA left) is compared to normal thyroid tissue (safe tissue reference) obtained from a patient who underwent total thyroidectomy for a laryngeal carcinoma that partially invaded the thyroid gland, to search for microRNA signatures of perilesional tissues (80 miRNA microarray slides).Experiments is performed with a miRNA microarray, referenced in GEO under the accession number GPL4717 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GPL4717).
Project description:Context: Papillary thyroid cancer (PTC) is the most common thyroid cancer with dramatically increasing worldwide. Accurate diagnosis is crucial to avoid unnecessary overtreatment for low-risk patients, but the currently available markers are still insufficient. tRNA-derived fragments (tRFs) are emerging as a new class of small non-coding RNAs due to their potential roles as novel biomarkers and therapeutic targets in cancer. However, their involvement in papillary thyroid carcinoma (PTC) is still unclear. Objectives: This study was performed to identify differentially expressed tRFs in PTC and investigate the role of serum tRFs to discriminate PTC from nodular goiters (NGs).Methods and Materials: tRF expression profiles were measured in pooled sera from patients with PTCs (n=6), NGs (n=6) and healthy subjects (n=6) using high-throughput sequencing (cohort1). One selected tRF candidate was validated in the same individual samples (cohort1) by qRT-PCR. The confirmed tRF was further validated in a larger second cohort including patients with PTCs (n=30), NGs (n=20) and healthy individuals (n=18).Results: Our sequencing results showed that circulating tRFs were differentially expressed in patients with PTC compared with those with NG and healthy people. After the validation in individual samples, tRF-Pro-AGG-018 was confirmed as differentially elevated in serum samples of patients with PTC. These results were further confirmed in a larger second cohort. Moreover, tRF-Pro-AGG-018 exhibited good diagnostic performance with a sensitivity of 0.7222 and a specificity of 0.8846 for PTC and it was associated with several targeted genes of PTC. Conclusions: Our study identified that the serum tRFs were differentially expressed in PTC compared with NG and healthy individuals. Notably, circulating tRF-Pro-AGG-018 was found to have a significant elevation in patients with PTC and exhibited good diagnostic performance with relatively high sensitivity and specificity for PTC. Our findings suggest tRFs might serve as novel circulating biomarkers in predicting patients with PTC, which may prevent unnecessary thyroid surgeries for low-risk and benefit from optimal
Project description:Thyroid ultrasound and ultrasound-guided fine-needle aspiration (USG/FNA) biopsy are currently used for diagnosing papillary thyroid carcinoma (PTC), but their detection limit could be improved by combining other biomarkers. To discover novel PTC biomarkers, we herein applied a GeLC-MS/MS strategy to analyze the proteome profiles of serum-abundant-protein-depleted FNA cystic fluid from benign and PTC patients, as well as two PTC cell line secretomes. From them, we identified 346, 488, and 2105 proteins, respectively. Comparative analysis revealed that 191 proteins were detected in the PTC but not the benign cystic fluid samples, and thus may represent potential PTC biomarkers. Among these proteins, 101 were detected in the PTC cell line secretomes, and seven of them (NPC2, CTSC, AGRN, GPNMB, DPP4, ERAP2, and SH3BGRL3) were reported in public PTC transcriptome datasets as having 4681 elevated mRNA expression in PTC. Immunoblot analysis confirmed the elevated expression levels of five proteins (NPC2, CTSC, GPNMB, DPP4, and ERAP2) in PTC versus benign cystic fluids. Immunohistochemical studies from near 100 pairs of PTC tissue and their adjacent non-tumor counterparts further showed that AGRN (n = 98), CTSC (n = 99), ERAP2 (n = 98) and GPNMB (n = 100) were significantly (p<0.05) overexpressed in PTC and higher expression levels of AGRN and CTSC were also significantly associated with metastasis and poor prognosis of PTC patients. Collectively, our results indicate that an integrated analysis of FNA cystic fluid proteome, cancer cell secretome and tissue transcriptome datasets represents a useful strategy for efficiently discovering novel PTC biomarker candidates.
Project description:Long noncoding RNAs (lncRNAs) have been shown to play a significant role in cancer biology. The aim of this study was to determine roles of lncRNAs in differences of clinical features related to the of papillary thyroid carcinoma (PTC) patients with or without Hashimoto's thyroiditis (HT). In the present study, we detected the differentially expressed lncRNAs in tumor tissues of PTC with or without HT by lncRNA microarrays. qRT-PCR, cell viability assay, cell cycle analysis and bioinformatics tools were used to verify and analyze the data. We found that 1031 lncRNAs and 1338 mRNAs were abnormally expressed in 10 tissue samples of PTC complicated with HT compared to pure PTC. Gene Ontology and pathway analyses of the mRNAs suggested that several biological processes and pathways, especially immune system processes, were promoted in PTC complicated with HT. Twenty lncRNAs were verified in 31 PTC complicated with HT and 64 pure PTC specimens using qRT-PCR, and the results were consistent with the microarrays data. Specifically, ENST00000452578, a down-regulated lncRNA in PTC complicated with HT, was negatively correlated with tumor size. Cell viability assay revealed that ENST00000452578 could inhibit cell proliferation. Co-expression analysis revealed that PPM1H, an mRNA regulated by ENST00000452578, may play an important role in cell cycle arrest. Our results indicate that lncRNAs and mRNAs plays an important role in the different clinical characteristics of PTC patients with or without HT, which might provide new insight from the perspective of RNA into the understanding of the cancers.
Project description:Anaplastic thyroid carcinoma (ATC) is a rare but deadly thyroid cancer. In contrast, papillary thyroid carcinoma (PTC) is common and highly curable. Minimally invasive biomarkers are needed to distinguish ATC and PTC. Here, by small RNA-seq we show the differential expression levels of several miRNAs, which include miR-34a and miR-210 in ATC compared to PTC cell lines.