MiR-205-5p/GGCT Attenuates Growth and Metastasis of Papillary Thyroid Cancer by Regulating CD44.

Papillary thyroid cancer (PTC) remains the most common endocrine malignancy, despite marked achieves in recent decades, and the mechanisms underlying the pathogenesis and progression for PTC are incompletely elucidated. Accumulating evidence show that γ-glutamylcyclotransferase (GGCT), an enzyme participating in glutathione homeostasis and is elevated in multiple types of tumors, represents an attractive therapeutic target. Using bioinformatics, immunohistochemistry, qRT-PCR, and Western blot assays, we found that GGCT expression was upregulated in PTC and correlated with more aggressive clinicopathological characteristics and worse prognosis. GGCT knockdown inhibited the growth and metastasis ability of PTC cells both in vitro and in vivo and reduced the expression of mesenchymal markers (N-cadherin, CD44, MMP2, and MMP9) while increasing epithelial marker (E-cadherin) in PTC cells. We confirmed binding of microRNA-205-5p (miR-205-5p) on the 3'-UTR regions of GGCT by dual-luciferase reporter assay and RNA-RNA pull-down assay. Delivery of miR-205-5p reversed the pro-malignant capacity of GGCT both in vitro and in vivo. Lastly, we found that GGCT interacted with and stabilized CD44 in PTC cells by co-immunoprecipitation and immunohistochemistry assays. Our findings illustrate a novel signaling pathway, miR-205-5p/GGCT/CD44, that involves in the carcinogenesis and progression of PTC. Development of miR-205-mimics or GGCT inhibitors as potential therapeutics for PTC may have remarkable applications.

S100A1 is a Potential Biomarker for Papillary Thyroid Carcinoma Diagnosis and Prognosis.

S100 calcium binding protein A1 (S100A1) is an important member of the S100 family and known to express in a variety of cancers. However, the biological functions of S100A1 in thyroid carcinoma have not been thoroughly studied. In this report, bioinformatics analyses and immunohistochemistry assays were applied to assess the expression profile of S100A1 as well as its relationship with the pathological features and prognosis of papillary thyroid carcinoma (PTC). Meanwhile, functions of S100A1 in PTC cells were analyzed with either in vitro or in vivo experiments. S100A1 was significantly up-regulated in PTC tissues compared with adjacent non-cancerous tissues. S100A1 protein expression was significantly associated with tumor size (p=0.0032) or lymph node metastasis (p=0.0331). More importantly, an elevated S100A1 expression was significantly correlated with a worse recurrence-free survival (RFS) (HR=2.26, p=0.042). Further, knockdown of S100A1 dramatically inhibited cell proliferation and migration as well as increased apoptosis of PTC cells. S100A1 knockdown inhibited tumor progression as seen in in vivo experiments. In terms of mechanism, down-regulation of S100A1 induced yes associated protein (YAP) phosphorylation in the cytoplasm and diminished Hippo/YAP pathway activation. Therefore, S100A1 may serve as a novel oncogene and a promising biomarker for PTC diagnosis and prognosis.

ZW10 interacting kinetochore protein may serve as a prognostic biomarker for human breast cancer: An integrated bioinformatics analysis.

ZW10 interacting kinetochore protein (ZWINT) is an essential component for the mitotic spindle checkpoint and has been reported to be upregulated in numerous types of human cancer. Nonetheless, its role in breast cancer (BC) remains unclear. Herein, it was demonstrated that the expression of ZWINT was significantly higher in BC than in normal breast tissues, on the basis of integrated analysis of bioinformatics studies, cancer database analyses and immunohistochemical detection. Elevated ZWINT levels were associated with a number of clinicopathological characteristics in patients with BC. These characteristics include: i) Positive human epidermal growth factor receptor 2 expression; ii) triple-negative BC; iii) younger age; iv) basal-like subtype; and v) greater Scarff-Bloom-Richardson grades. Additionally, prognostic analysis indicated that shorter relapse-free survival, overall survival and metastatic relapse-free survival may be associated with high ZWINT expression. A total of 16 pathways associated with high ZWINT expression, including Myc targets V1/2, DNA repair and mitotic spindle pathways, were identified using Gene Set Enrichment Analysis. In addition, a positive correlation between cyclin-dependent kinase 1 (CDK1) and ZWINT mRNA expression was identified by co-expression analysis. The present study suggested that ZWINT may serve as an effective prognostic biomarker for BC. In addition, ZWINT may be implicated in the CDK1-mediated initiation and progression of BC. However, further research is required to understand the role of ZWINT in BC.