ABSTRACT
OBJECTIVE: The aim of this study was to determine the role of microRNA-506-3p (miR-506) in papillary thyroid carcinoma (PTC), and to further explore the underlying mechanism. PATIENTS AND METHODS: The expression level of miR-506 in clinical cases was detected by Real Time-fluorescence quantitative Polymerase Chain Reaction (RT-qPCR). Meanwhile, RT-qPCR was performed to determine miR-506 expression in different PTC cell lines. Bioinformatics software was used to predict the possible target genes of miR-506. Dual-Luciferase reporter gene assay together with Western blot (WB) assay were used to verify the prediction results. Finally, cellular functions such as proliferation and metastasis capacities were detected in vitro. RESULTS: RT-qPCR was used to measure the expression level of miR-506 in 80 paired PTC cases. The results showed that the expression level of miR-506 in PTC tissues was significantly decreased. In vitro, miR-506 expression was also markedly suppressed in four PTC cell lines. TPC-1 cells expressed the lowest level of miR-506. Subsequently, the target gene of miR-506 was predicted by TargetScan, miRBase and miRanda. The prediction results indicated that IL17RD was an alternative target gene of miR-506. Furthermore, miR-506 was found to remarkably inhibit the Luciferase activity of wild-type IL17RD. However, it had no effect on mutant-type. Besides, the protein expression level of IL17RD was significantly reduced in miR-506-overexpressing TPC-1 cells. More importantly, the restored expression of IL17RD could alleviate the blocking effects of miR-506 on cell proliferation, migration and invasion. CONCLUSIONS: In this study, we found that miR-506 could inhibit the proliferation and metastasis of PTC cells. Meanwhile, IL17RD might be a downstream target of the biological process. Our findings provided a new therapeutic direction for the treatment of PTC.
Subject(s)
Carcinoma, Papillary/genetics , Cell Proliferation , MicroRNAs/genetics , Thyroid Neoplasms/pathology , Carcinoma, Papillary/secondary , Cell Line, Tumor , Cell Movement , Computational Biology , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , Humans , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/pathology , Neoplasm Metastasis/genetics , Predictive Value of Tests , Receptors, Interleukin/metabolism , Thyroid Cancer, Papillary/pathologyABSTRACT
Galectin-1 (Gal-1) is involved in several pathological activities associated with tumor progression and chemoresistance, however, the role and molecular mechanism of Gal-1 activity in hepatocellular carcinoma (HCC) epithelial-mesenchymal transition (EMT) and sorafenib resistance remain enigmatic. In the present study, forced Gal-1 expression promoted HCC progression and sorafenib resistance. Gal-1 elevated αvß3-integrin expression, leading to AKT activation. Moreover, Gal-1 overexpression induced HCC cell EMT via PI3K/AKT cascade activation. Clinically, our data revealed that Gal-1 overexpression is correlated with poor HCC survival outcomes and sorafenib response. These data suggest that Gal-1 may be a potential therapeutic target for HCC and a biomarker for predicting response to sorafenib treatment.
Subject(s)
Epithelial-Mesenchymal Transition/drug effects , Focal Adhesion Kinase 1/metabolism , Galectin 1/metabolism , Niacinamide/analogs & derivatives , Phenylurea Compounds/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Animals , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Chromones/pharmacology , Drug Resistance, Neoplasm/drug effects , Galectin 1/antagonists & inhibitors , Galectin 1/genetics , Humans , Integrin alphaVbeta3/antagonists & inhibitors , Integrin alphaVbeta3/genetics , Integrin alphaVbeta3/metabolism , Liver Neoplasms/drug therapy , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Nude , Morpholines/pharmacology , Neoplasm Invasiveness , Niacinamide/pharmacology , Niacinamide/therapeutic use , Phenylurea Compounds/therapeutic use , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , RNA Interference , Signal Transduction/drug effects , Sorafenib , Survival RateABSTRACT
A method using a molecularly imprinted polymer (MIP) as the selective sorbent for solid-phase extraction (SPE) has been developed. Its application to the assay of hairy nicotine level among smokers and non-smokers with high-performance liquid chromatography (HPLC) and evaluation of exposures to the environmental tobacco smoke (ETS) were validated. The MIP was synthesized using nicotine as the template molecule and methacrylic acid (MAA) as the functional monomer. This MIP-SPE method provided inherent selectivity and a sensitive response to nicotine with a detection limit of 0.2 ng/ml hair at a signal-to-noise ratio of 3:1 and the limit of quantification was 0.5 ng/ml. The linearity was assessed in the range of 0.5-80 ng/ml hair, with a coefficient (r(2)) greater than 0.987. The amounts of nicotine determined in smokers and non-smokers hair were in the range of 5.1-69.5 ng/mg hair and 0.50-9.3 ng/mg hair, respectively. The reported measures of ETS exposure were significantly associated with hairy nicotine levels. This assay of nicotine in hair using MISPE provided a very selective and reliable method for the evaluation of the exposure to tobacco smoke.
