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Pulmonary fibrosis (PF) is one of the most prevalent causes of death following paraquat (PQ) poisoning. As demonstrated in previous studies by the present authors, epithelial-to-mesenchymal transition (EMT) is associated with PQ‑induced PF. In addition, hypoxia‑inducible factor‑1α (HIF‑1α) and lysyl oxidase (LOX) promote EMT following PQ poisoning. However, the association between HIF‑1α‑ and LOX‑mediated regulation of EMT remains unclear. The present study investigated the association between HIF‑1α and LOX with regard to PQ‑induced EMT. A549 and RLE‑6TN cells were treated with PQ, and HIF‑1α and LOX expression was silenced with short interfering RNAs. Changes in the expression of HIF‑1α, LOX, β‑catenin and EMT‑related makers were detected using real‑time quantitative polymerase chain reaction, immunofluorescence, and western blotting. HIF‑1α and LOX were associated with PQ‑induced EMT, and their expression levels were significantly increased (P<0.05). LOX expression was significantly decreased following PQ poisoning when HIF‑1α expression was inhibited (P<0.05). However, the level of HIF‑1α did not change significantly when LOX was silenced. The expression level of β‑catenin and the degree of EMT were significantly decreased following HIF‑1α and LOX silencing in both cell lines (P<0.05). The association between HIF‑1α and LOX in regulating EMT during PQ‑induced PF may be unidirectional. HIF‑1α may regulate PQ‑induced EMT through the LOX/β‑catenin pathway. [ABSTRACT FROM AUTHOR]

Clear cell renal cell carcinoma (ccRCC) represents the most common type of kidney cancer with high mortality in its advanced stages. Our study aim was to explore the correlation between tumor epithelial-to-mesenchymal transition (EMT) and patient survival. Renal biopsies of tumorous and adjacent nontumorous tissue were taken with a 16 g needle from our patients (n = 26) undergoing partial or radical nephrectomy due to ccRCC. RNA sequencing libraries were generated using Illumina TruSeq® Access library preparation protocol and TruSeq Small RNA library preparation kit. Next generation sequencing (NGS) was performed on Illumina HiSeq2500. Comparative analysis of matched sample pairs was done using the Bioconductor Limma/voom R-package. Liquid chromatography-tandem mass spectrometry and immunohistochemistry were applied to measure and visualize protein abundance. We detected an increased generic EMT transcript score in ccRCC. Gene expression analysis showed augmented abundance of AXL and MMP14, as well as downregulated expression of KL (klotho). Moreover, microRNA analyses demonstrated a positive expression correlation of miR-34a and its targets MMP14 and AXL. Survival analysis based on a subset of genes from our list EMTrelated genes in a publicly available dataset showed that the EMT genes correlated with ccRCC patient survival. Several of these genes also play a known role in fibrosis. Accordingly, recently published classifiers of solid organ fibrosis correctly identified EMT-affected tumor samples and were correlated with patient survival. EMT in ccRCC linked to fibrosis is associated with worse survival and may represent a target for novel therapeutic interventions. [ABSTRACT FROM AUTHOR]