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Six-transmembrane epithelial antigen of the prostate 1 (STEAP1), a member of the STEAP family, is a general tumor antigen. However, no information has been available to date regarding the function of STEAP1 in the progression of endometrial carcinoma. In this study, we used in vitro and in vivo strategies to prove that STEAP1 plays an important role in the progression of endometrial carcinoma. Immunohistochemistry, immunocytochemistry, quantitative reverse transcription polymerase chain reaction (RT-qPCR), and Western blot analysis were used to detect the expression of STEAP1 in normal endometrial cells and endometrial cancer cell lines. The progression of the cell cycle, plate clone formation assay, and transwell migration and invasion assays were performed to examine the effects of STEAP1 on cell proliferation, clonogenicity, migration, and their invasive capacity. In addition, we confirmed that STEAP1 was tightly correlated with the development of tumor in vivo. The relationship between epithelial to mesenchymal transition (EMT) and STEAP1 expression was evaluated by RT-qPCR and Western blot analysis. Matrix metalloproteinase (MMP) zymography assay was used to detect the activities of MMP2 and MMP9. STEAP1 was restrictively expressed in endometrial carcinoma and downregulation of the STEAP1 gene increased proliferation and clonogenicity, as well as promoted cell migration, invasion, and the progress of EMT. STEAP1 is downregulated in endometrial carcinoma and can restrict migration and invasion of endometrial carcinoma cells. Overall, STEAP1 may be an ideal target for tumor therapy and diagnosis in the future. K E Y W O R D S endometrial carcinoma, epithelial to mesenchymal transition, invasion, migration, six-transmembrane epithelial antigen of the prostate 1A standard streptavidin-biotin-peroxidase staining procedure was used, wherein formalin-fixed, paraffin-embedded endometrial tissues were cut into 5-μm slices. After a series of processing steps, such as dewaxing in xylene, rehydration, and antigen retrieval, sections were incubated with the mouse anti-human STEAP1 monoclonal antibody (ab117454; Abcam) at a dilution of 1﹕200 . Six-transmembrane epithelial antigen of the prostate 1 is associated with tumor invasion and migration in endometrial carcinomas.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been identified previously in the pathogenesis of hypertension and some gestational diseases. However, the biological functions of MALAT1 in pregnancy-induced hypertension (PIH) are still poorly understood. Herein, we aim to explore the functional relevance of MALAT1 in PIH and to explain the potential underlying mechanisms. We found that the levels of ET-1 and MALAT1 were upregulated and that of miR-150-5p were downregulated in the serum of pregnant women with PIH and the aortic endothelial cells (ECs) of reduced uterine perfusion pressure (RUPP)-induced rat models. In aortic ECs, MALAT1 could competitively bind to miR-150-5p to upregulate the expression of ET-1. The MALAT1/ miR-150-5p/ET-1 axis regulated the expression of endothelin B receptor (ETBR) in aortic ECs leading to oxidative stress imbalance and increased the release of proinflammatory cytokines (IL-18 and IL-1β), which concurrently activated the NF-κB pathway to regulate the ETBR expression and to stimulate smooth muscle cell (SMC) contraction. Furthermore, silencing MALAT1 could alleviate the hypertensive symptoms of RUPP-induced rat models. Taken conjointly, the upregulation of MALAT1 can reduce the expression of ET-1 by competitively binding to miR-150-5p, which enhances the expression of ETBR via the activation of the NF-κB pathway in SMCs, thus exacerbating the hypertensive symptoms in the RUPP-induced rat models. K E Y W O R D Sendothelial cells, endothelin-1, metastasis-associated lung adenocarcinoma transcript 1, microRNA-150-5p, NF-κB pathway, pregnancy-induced hypertension, smooth muscle cells

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Background Chelidonium majus L. (C. majus) belongs to the Papaveridae family and is the dried whole grass of C. majus. It is usually used in clinical practice of traditional Chinese medicine and has been reported of the effect in relieving cough and asthma. However, the mechanism of action is still unknown. This research aimed to illuminate the therapeutic effect of C. majus in the inhibition of allergic asthma. Methods Asthmatic SD rats were first sensitized and established through ovalbumin (OVA) motivation. Subsequently, lung histopathological analysis (HE, Masson, PAS) and inflammatory cytokines assay (IL-4, IL-17, IL-6) were implemented to evaluate the protective effects of C. majus on asthma. Then, the effects of C. majus and their molecular mechanisms of action on asthma were detected based on the integration of transcriptomics and metabolomics analyses. Results After administration with C. majus, the histological injury of inflammation, collagen deposition and mucus secretion in lungs were attenuated and the serum inflammatory cytokines perturbations were also converted. Furthermore, integrated analysis revealed that after C. majus treatment, 7 different expression genes (DEGs) (Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9) and 9 metabolic biomarkers (ADP, Xanthosine, Hypoxanthine, Inosine, prostaglandin E2 (PGE2), prostaglandin F2a (PGF2a), phosphatidylserine, Creatine and LysoPC(10:0)) were discovered to be connected with the enrichment metabolic pathways, including Purine metabolism, Arachidonic acid metabolism, Arginine and proline metabolism and Glycerophospholipid metabolism. The obtained metabolic biomarkers and DEGs are mainly related to energy metabolism and inflammation, and may be potential therapeutic targets. Conclusion C. majus relieved OVA-induced asthma in rats by regulating the Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9 genes expression to restore the disorders in energy metabolism and inflammation.