Background/Aims: miR-146a has recently been shown to promote cell proliferation, migration, and invasion in many cancers, but the role of miR-146a in clear cell renal cell carcinoma (ccRCC) remains unclear. Methods: Reverse transcription quantitative PCR (RT-qPCR) was performed to investigate the mRNA expression of miR-146a and CADM2 in ccRCC tissues. The luciferase reporter assay, Western blotting, and ChIP assay were carried out to explore the promoter and the transcription factor of miR-146a. Moreover, the effect of miR-146a and CADM2 on ccRCC cells was explored using methyl thiazolyl tetrazolium, colony formation, and migration and invasion assays. The luciferase reporter assay, RT-qPCR, western blotting, and immunofluorescence assay were carried out to investigate whether CADM2 is directly regulated by miR-146a. A tumor xenograft model and immunohistochemical staining were used to examine the carcinogenic effect of miR-146a and CADM2 in vivo. Results: miR-146a has been shown to promote cell proliferation, migration, and invasion. Here, we found that miR-146a is highly expressed in ccRCC tissues, whereas CADM2 is down-regulated. Hypoxia can induce the expression of miR-146a by stimulating its promoter. In addition, we demonstrated that miR-146a promoted and CADM2 inhibited proliferation, migration, and invasion of ccRCC cells. The 3’ untranslated region (UTR) luciferase reporter assay identified that miR-146a targeted the 3’ UTR of CADM2 and negatively regulated its expression. Ectopic expression of CADM2 counteracted the promoting effect of miR-146a on cell proliferation, migration, invasion, and the epithelial–mesenchymal transition process. Conclusion: Together, the finding of down-regulation of CADM2 by miR-146a can provide new insights into ccRCC pathogenesis and might contribute to the development of novel therapeutic strategies.
Cerebral edema and elevated intracranial pressure (ICP) are common complications observed following ischemic stroke. Osmotherapy has been used as a foundation to manage ICP induced by cerebral edema, and albumin is one of the most commonly used osmotic agents. The present study aimed to explore whether albumin lowered ICP by reducing cerebral edema when albumin elevated the colloid osmotic pressure (COP) of plasma. Sprague‑Dawley rats that underwent middle cerebral artery occlusion were used to assess COP and ICP. Magnetic resonance imaging measurements were performed to evaluate the cerebral edema and infarct size. Evans blue was used to assess the blood‑brain barrier (BBB) permeability. Western blotting was used to determine the expression levels of the tight junction proteins in cerebral vascular endothelial cells. The results showed that 25% albumin treatment (1.25 g/kg) by intravenous injection elevated the COP of plasma but did not reduce the ICP in rats that had undergone ischemic stroke. Additionally, albumin did not reduce the infarct size and instead aggravated the cerebral edema. Furthermore, the BBB permeability was increased by albumin. Concomitantly, albumin treatment significantly downregulated the expression of tight junction proteins (ZO‑1, occludin and claudin‑5) in cerebral vascular endothelial cells. Tight junction protein expression was significantly upregulated when the cells were treated with an MMP‑9 inhibitor (GM6001). These results suggest that albumin aggravates cerebral edema in rats with ischemic stroke by increasing BBB permeability.
Archaeological fieldwork at the fortified site of Kuiyukexiehai'er (Koyuk Shahri) in the Xinjiang Uygur Autonomous Region of north-western China yields the earliest known evidence for urban occupation in the Tarim Basin, providing new insights into early urbanism and agro-pastoral subsistence practices in the region during the first millennium BC.
Background. Dead end 1 (DND1) plays a vital role during oncogenesis and cancer progression by regulating the mRNA content via competitive combination with miRNA, but what function it exerts in prostate cancer has been unclear. The purpose of this paper is to explore the correlation between DND1 expression levels and clinical characteristics in prostate cancer (PCa) patients. Materials and Methods. To assess the expression of DND1 in tumor specimens compared with paired paracancerous tissues, the sample from 83 patients was analyzed by immunohistochemistry. The Cancer Genome Atlas (TCGA) database was used to verify our results. Subsequently, we statistically analyzed the relationship between DND1 expression and the clinical prognosis of PCa patients. Results. Compared with paracancerous tissues, DND1 has a higher expression level in prostate cancer. The overexpression of DND1 in protein level was significantly associated with the higher clinical stage ( P = 0.006 ), ISUP grading group ( P < 0.001 ), seminal vesicle invasion ( P = 0.006 ), and PSA density ( P = 0.002 ). Furthermore, the overexpression of DND1 indicates a poor clinical prognosis in prostate cancer patients. Conclusion. High-level expression of DND1 was associated with tumor progression and poor clinical prognosis. Hence, DND1 may become a potential prognostic biomarker for PCa.
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