Phosphoinositide-dependent kinase 1-associated glycolysis is regulated by miR-409-3p in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most popular kidney cancer in adults. Metabolic shift toward aerobic glycolysis is a fundamental factor for ccRCC therapy. MicroRNAs (miRNAs) are thought to be important regulators in ccRCC development and progression. Phosphoinositide-dependent kinase 1 (PDK1) is required for metabolic activation; however, the role of PDK1-induced glycolytic metabolism regulated by miRNAs is unclear in ccRCC. So, the purpose of the current study is to elucidate the underlying mechanism in ccRCC cell metabolism mediated by PDK1. Our results revealed that miR-409-3p inhibited glycolysis by regulating PDK1 expression in ccRCC cells. We also found that miR-409-3p was regulated by hypoxia. Our results indicated that PDK1 facilitated ccRCC cell glycolysis, regulated by miR-409-3p in hypoxia.

Role of miR-486-5p in regulating renal cell carcinoma cell proliferation and apoptosis via TGF-ß-activated kinase 1.

Renal cell carcinoma (RCC) is a common kidney tumor in adults. The role of miR-486-5p in RCC is unknown. The aim of our study was to identify new targets regulated by miR-486-5p in RCC, to obtain a deeper insight into the network and to better understand the role of these microRNAs and their targets in carcinogenesis of RCC. We performed a series of tests and found consistently lower expression levels of miR-486-5p in kidney cancer cells. Restoration of miR-486-5p expression in RCC cells could lead to the suppression of cell proliferation and the increase of cell apoptosis. Further studies demonstrated that TGF-ß-activated kinase 1 was a target gene of miR-486-5p in kidney cancer cells. It was also shown that C-C motif chemokine ligand 2 (CCL2) from tumor-associated macrophages downregulated miR-486-5p expression, and miR-486-5p inhibited RCC cell proliferation and apoptosis resistance induced by CCL2. The study demonstrates that there are potential diagnosis and therapy values of miR-486-5p in RCC.

Role of Protease-Activated Receptor 2 in Regulating Focal Segmental Glomerulosclerosis.

Background /Aims: The underlying mechanisms leading to focal segmental glomerulosclerosis (FSGS) are lacking. In this report, we examined the role of protease-activated receptors (PARs) subtype PAR2 and its downstream signals in regulating the pathophysiological process of FSGS. METHODS: Nephropathy was induced by intravenous injections of adriamycin (ADR) in rats to study FSGS. Western Blot analysis and ELISA were employed to determine the protein expression levels of PAR2 and its downstream signal pathways as well as the levels of PICs. RESULTS: In ADR rats, expression of PAR2, PKCε and PKA was amplified and this was accompanied with increases of pro-inflammatory cytokines (PICs) including IL-1ß, IL-6 and TNF-α. Inhibition of PAR2 signal by systemic administration of FSLLRY-NH2 (FSL) attenuated amplification of PICs. Notably, FSL further influenced key molecular mediators during development of FSGS. i.e., it specifically restored the impaired nephrin and attenuated the exaggerated transforming growth factor beta 1 (TGF-ß1), caspase-9 and desmin thereby improving worsened renal functions and glomerular injury. Consistent with this, in cultured podocytes FSL also largely restored downregulation of nephrin and attenuated amplifications of caspase-9 and desmin induced by TGF-ß1. CONCLUSIONS: Results of this study suggest that PAR2 plays an important role in mediating renal injury induced by glomerulosclerosis. Inhibition of PAR2 signal pathway has a protective effect on FSGS mainly via PIC and TGF-ß1 mechanisms. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of FSGS observed in patients.

Rare cases of pulmonary inflammatory myofibroblastic tumors in adult male patients: a case report.

Pulmonary inflammatory myofibroblastic tumors (IMTs) are rarely reported in adult males. Given the low incidence of IMT and the lack of imaging references and pathological guidance, the misdiagnosis rate of IMT is high. In this article, we describe two cases of IMTs in the lungs. Both patients were adult males with lesions in the right lobe, a history of pulmonary tuberculosis, and a long period of refractory intermittent pulmonary inflammation. Our two male patients both experienced intermittent cough symptoms, but pulmonary IMTs were not suspected for a long time. Both patients were diagnosed with pulmonary tuberculosis before IMT was confirmed and treated with isoniazid (H), rifampin (R), pyrazinamide (Z), and ethambutol (E) (HRZE) or isoniazid (H), levofloxacin (L), pyrazinamide (Z), and ethambutol (E) (HLZE) for months. In Case 2, we observed multiple subpleural cord signs in the left lung, soft tissue mass shadows at the apex of the right upper lobe, a thickened interlobular interval, and scattered patches and nodules in the upper right lung. These features are novel in the identification of IMTs. Both of the pathological findings revealed a great deal of myofibroblasts, fibroblasts and collagen fibers in the lower right lung lesion, accompanied by a large number of plasma cells and foam cell infiltration, which were consistent with the features of IMT. The two patients displayed exceedingly different symptoms, computed tomography (CT) imaging features, and pathological results from those reported in traditional records. These findings provide novel references that will extend understandings of this rare disease.