Clear cell renal cell carcinoma (ccRCC) is the most common RCC subtype with high metastasis, poor prognosis and conventional chemotherapy resistance. Prostate cancer associated transcript 1 (PCAT1) is an important lncRNA that was reported to be involved in cell proliferation, migration and invasion of several types of cancer cells. However, its role in ccRCC is still undetermined. This study found that PCAT1 levels were elevated in ccRCC tumors as well as several ccRCC cells, and knockdown of PCAT1 with siRNA (si-PCAT1) alleviated cell proliferation, migration and invasion of Caki-2 and ACHN cells. With bioinformatics analysis, dual-luciferase reported assay, RNA pull-down assay and Spearman's correlation analysis, we demonstrated that PCAT1 acted as a sponge for miR-656 and miR-539. Moreover, we found dual competitive interaction of miR-656/539 with PCAT1 and yes-associated protein (YAP), resulting in the identification of PCAT1-miR-656/539-YAP axis in Caki-2 and ACHN cells. With CCK-8 assay and transwell assay, miR-656/539 inhibitor or YAP overexpression could alleviate the effects of si-PCAT1 on the proliferation, migration and invasion of Caki-2 and ACHN cells. Our data indicated that PCAT1 promotes proliferation, migration and invasion of ccRCC cells by upregulating YAP via sponging miR-656 and miR-539. Taken together, this study provided a novel therapeutic target for ccRCC treatment.
BackgroundParaquat is a major cause of fatal poisoning after ingestion in many parts of Asia and the Pacific nations. However, optimal prognostic indicators to evaluate patient mortality have not been unequivocally established. Following acute paraquat poisoning, a number of amino acids (AA), are abnormally expressed in metabolic pathways. However, the alterations in AA metabolite levels after paraquat poisoning remain unknown in humans.Material/MethodsIn the present study, 40 patients were enrolled, of whom 16 survived and 24 died. A metabolomics approach was used to assess changes in AA metabolites in plasma and its potential prognostic value following paraquat poisoning. Mass spectrometry (MS) based on metabolite identification was conducted.ResultsTwenty-five AA levels in plasma were abnormally expressed in non-survivor patients. Among them, creatinine, indolelactate, and 3-(4-hydroxyphenyl)lactate were found to be highly correlated with paraquat death prediction. It was noted that the intensity levels of these 3 AA metabolites in the non-survivor group were substantially higher than in the survivor group. Furthermore, we examined receiver operating characteristic (ROC) curves for clinical validation. ROC results showed that 3-(4-hydroxyphenyl)lactate had the highest AUC of 0.84, while indolelactate and creatinine had AUCs of 0.75 and 0.83, respectively, suggesting that they can be used to predict the clinical outcome (although this methodology is expensive to implement).ConclusionsMetabolic profiling of AA levels could be a reliable tool to identify effective indicators for the early high precision prognosis of paraquat poisoning.
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