Taken together, the results suggest that miR-222 promotes tumor invasion and metastasis in thyroid cancer by targeting PPP2R2A. Thus, miR-222 could serve as a potential diagnostic biomarker, as well as an attractive therapeutic tool for thyroid cancer.

Highlights d BDNF-AS induces tamoxifen resistance and malignant progression of breast cancers d BDNF-AS driven by MEF2A-regulated enhancer acts as scaffold of RNH1/TRIM21 d BDNF-AS activates mTOR pathway by abolishing RNH1regulated mTOR mRNA decay

Background: It is well known that the dysregulation of microRNAs (miRNAs) has been identified in papillary thyroid carcinoma (PTC), but their roles in the progression and metastasis of PTC remain unclear. is associated with cancer progression as an oncogene which is predicted to target at the Wnt/β-catenin signaling pathway. Our study aimed to investigate the role of miR-3619-3p on PTC cell migration and invasion, as well as the underlying mechanisms. Methods:The expression of miR-3619-3p in 36 PTC tissues and corresponding tumor-adjacent tissues, as well as 3 PTC cell lines (BCPAP, K1, TPC-1) and the normal thyroid epithelial cell line (N-thy-ori 3-1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between miR-3619-3p expression and clinicopathologic status of PTC patients was analyzed. Migration, invasion, and wound healing, were used to evaluate the role of miR-3619-3p in PTC. The activation of β-catenin and the possible molecular pathway were detected by western blotting. Results:The expression of miR-3619-3p in PTC tissues was significantly higher than the corresponding tumor-adjacent tissues (P<0.01), and its high expression positively correlated with extrathyroidal invasion, multicentricity, and cervical lymph node metastasis. Moreover, the miR-3619-3p was also up-regulated in PTC cell lines when compared to N-thy-ori 3-1. MiR-3619-3p enhanced the capabilities of migration and invasion in PTC cell lines. Furthermore, miR-3619-3p activated Wnt/β-catenin pathway via maintaining the mRNA stability of β-catenin.Conclusions: miR-3619-3p promoted PTC cell migration and invasion as an oncogene via activating the Wnt/β-catenin pathway through increasing the stability of β-catenin.

Background. Ten-eleven translocation (TET) enzymes catalyze the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) promoting demethylation in cells. However, the expression pattern and biologic significance of TET in papillary thyroid carcinoma (PTC) remain unclear. This study aimed to elucidate the biological functions of TET1 and the miRNA and mRNA expression levels in PTC cells with downregulated TET1. Methods. The expression of the TET family in 49 PTC tissues and corresponding tumor-adjacent tissues, as well as PTC cell lines (BCPAP, K1, and TPC-1) and the normal thyroid epithelial cell line (Nthy-ori 3-1), were detected using quantitative real-time polymerase chain reaction. The 5hmC level was detected in PTC tissues and cell lines using immunohistochemistry and dot blot assay, respectively. After silencing the TET1 gene with siRNAs in BCPAP and TPC-1 cells, cell proliferation was detected using EdU assay. Transwell assay was used to investigate cell migration and invasion. miRNA and mRNA expression arrays were conducted in TET1-depleted BCPAP cells. Results. The expression level of TET1 decreased in PTC tissues and cell lines and was consistent with the reduction in the 5hmC level. The knockdown of the TET1 gene promoted cell migration and invasion in BCPAP cells. The expression of miR-7, miR-15/16 cluster, and let-7 family was downregulated, while the expression of let-7e was upregulated after siRNA-TET1 treatment in BCPAP cells. The expression of WNT4, FZD4, CDK6, MCF2L, and EDN1 was upregulated as potential target genes of dysregulated miRNAs. Conclusion. The study showed that TET1 dysfunction inhibited the migration and invasion of BCPAP cells and might have a potential role in the pathogenesis of PTC.

Background: Circulating cell-free DNA (cfDNA) serves as a biomarker in multiple malignant diseases.However, controversy still surrounds the role of cfDNA detection in the diagnosis and monitoring of papillary thyroid carcinoma (PTC). This study set out to identify the role of cfDNA detection in distinguishing between benign and malignant thyroid nodules.Methods: Tissue, blood cell, and plasma samples were collected from 10 patients with benign nodules and 10 patients with malignant nodules. The DNA isolated from these samples was subject to PCR-based amplification using primers designed for 50 proto-oncogenes and tumor suppressor genes. PCR products were sequenced using Illumina technology, and the mutations were detected with varScan among sequencing data for each sample and comparative analysis was carried out.Results: Through amplicon sequencing, we found one non-synonymous somatic mutation in the benign nodules and three in the malignant nodules. Among these four mutations, BRAF V600E mutation was detected in the tissue samples of 8 out of the 10 PTC patients, but it was not detected in the benign nodules.However, no BRAF V600E mutation was detected in cfDNA. Further differential analysis of cfDNA indicated that some genes had more mutations in benign patients than in malignant patients, such as MET and IDH, and some genes had more mutations in malignant patients, such as PIK3CA and EZH2.Conclusions: We found that BRAF V600E mutation was a credible disease-related mutation in PTC; however, it could not be detected in cfDNA. Moreover, there was a large difference in mutation gene distribution between benign and malignant thyroid nodules.