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Lysosomal dysfunction and impaired autophagic flux are involved in the pathogenesis of lipotoxicity in the kidney. Here, we investigated the role of transcription factor EB (TFEB), a master regulator of autophagy-lysosomal pathway, in palmitic acid induced renal tubular epithelial cells injury. We examined lipid accumulation, autophagic flux, expression of Ps211-TFEB, and nuclear translocation of TFEB in HK-2 cells overloaded with palmitic acid (PA). By utilizing immunohistochemistry, we detected TFEB expression in renal biopsy tissues from patients with diabetic nephropathy and normal renal tissue adjacent to surgically removed renal carcinoma (controls), as well as kidney tissues from rat fed with high-fat diet (HFD) and low-fat diet (LFD). We found significant lipid accumulation, increased apoptosis, accompanied with elevated Ps211-TFEB, decreased nuclear TFEB, reduced lysosome biogenesis and insufficient autophagy in HK-2 cells treated with PA. Kidney tissues from patients with diabetic nephropathy had lower nuclear and total levels of TFEB than that in control kidney tissues. Level of renal nuclear TFEB in HFD rats was also lower than that in LFD rats. Exogenous overexpression of TFEB increased the nuclear TFEB level in HK-2 cells treated with PA, promoted lysosomal biogenesis, improved autophagic flux, reduced lipid accumulation and apoptosis. Our results collectively indicate that PA is a strong inducer for TFEB phosphorylation modification at ser211 accompanied with lower nuclear translocation of TFEB. Impairment of TFEB-mediated lysosomal biogenesis and function by palmitic acid may lead to insufficient autophagy and promote HK-2 cells injury. • PA oversupply increased serine phosphorylation of TFEB at ser211 and reduces TFEB nuclear translocation in HK-2 cells. • Decreased nuclear distribution of TFEB ensuing impaired lysosomal biogenesis and insufficient autophagy. • The content of TFEB in renal tissue of diabetic nephropathy patients and HFD rats was lower than that of control group. • Overexpression of TFEB counteracts the impaired lysosome biogenisis and insufficient autophagy caused by PA intervention. [ABSTRACT FROM AUTHOR]

Abstract CircRNAs are reported to be implicated in the development of lung cancer. This study focused on assessing the expression, functions and molecular mechanism of circPUM1 in lung adenocarcinoma. Here, it showed that circPUM1 is significantly upregulated in both lung adenocarcinoma cell lines and tissues. Furthermore, silencing of circPUM1 impaired the proliferation, migration and invasion ability, and increased apoptosis in A549 cells. Nevertheless, overexpression of circPUM1 in SPC-A1 cells has the opposite effect. Silencing of circPUM1 inhibits the tumorigenesis in nude mice. Mechanistically, circPUM1 could sponge miR-326 and promote the expression of its downstream proteins Cyclin D1 and Bcl-2. In summary, this present study revealed that circPUM1 functions as an oncogene to promote the tumorigenesis of lung adenocarcinoma through circPUM1/miR-326/Cyclin D1 and Bcl-2 axis. This indicates that circPUM1 may act as a potential therapeutic target for lung adenocarcinoma. Highlights • Upregulation of circPUM1 in lung adenocarcinoma cell lines and tissues. • Silencing of circPUM1 inhibits the proliferation, migration, invasion and inhibited apoptosis in vitro, and vice versa. • CircPUM1 sponges miR-326 to upregulate Cyclin D1 and Bcl-2 expression to promote tumorigenesis. [ABSTRACT FROM AUTHOR]

MicroRNAs are a large class of tiny noncoding RNAs, which have emerged as critical regulators of gene expression, and thus are involved in multiple cellular processes, including cellular senescence. MicroRNA-33 has previously been established to exert crucial effect on cell proliferation, lipid metabolism and cholesterol metabolism. Nonetheless, the association between microRNA-33 and cellular senescence and its underlying molecular mechanism are far to be elucidated. The present study has attempted to probe into the effect of microRNA-33 on MEFs senescence. Our data unveiled that microRNA-33 was dramatically down-regulated in senescent MEFs compared to the young MEFs, and ectopic expression of microRNA-33 promoted MEFs senescence, while knock-down of microRNA-33 exhibited a protective effect against senescence phenotype. Moreover, we verified CDK6 as a direct target of microRNA-33 in mouse. Silencing of CDK6 induced the premature senescence phenotype of MEFs similarly as microRNA-33, while enforced expression of CDK6 significantly reverse the senescence-induction effect of microRNA-33. Taken together, our results suggested that microRNA-33 enhanced the replicative senescence of MEFs potentially by suppressing CDK6 expression. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs), characterized as single-stranded closed circular RNA molecules, have been established to exert pivotal functions in various biological or pathological processes. Nonetheless, the effects and underlying mechanisms concerning circRNAs on the aging and aging-related diseases remain elusive. We herein compared the expression patterns of circRNAs in young and senescent mouse embryonic fibroblasts (MEFs), and uncovered that circRNF169 was dramatically up-regulated in senescent MEFs compared with that in young MEFs. Therefore, we further digged into the role and potential mechanisms of circRNF169 in the senescence of MEFs. The results of senescence-associate-β-galactosidase staining and BrdU incorporation assay showed that silencing of circRNF169 significantly delayed MEFs senescence and promoted cell proliferation, while ectopic expression of circRNF169 exhibited the opposite effects. Moreover, the dual-luciferase reporter assay confirmed that circRNF169 acted as an endogenous miR-30c-5p sponge, which accelerated cellular senescence by sequestering and inhibiting miR-30c-5p activity. Taken together, our results suggested that circRNF169 exerted a crucial role in cellular senescence through sponging miR-30c-5p and represented a promising target for aging intervention. • CircRNF169 was dramatically up-regulated in senescent MEFs. • CircRNF169 significantly promoted the replicative senescence of MEFs. • CircRNF169 promoted the replicative senescence of MEFs through acting as a miR-30c-5p sponge. [ABSTRACT FROM AUTHOR]

Abstract: Vascular endothelial growth factor (VEGF) was investigated in the present study to see whether it could provide a therapeutic opportunity for the treatment of Alzheimer’s disease (AD). PDGF-hAPPV717I transgenic mice were treated with VEGF or PBS by intraperitoneal injection for three consecutive days. The results showed that VEGF ameliorated the memory impairment of mice, accompanied by CD34+ cells increasing in peripheral blood, vWF+ vessels increasing in hippocampus, and CD34+/VEGFR2+, vWF+/VEGFR2+ and BrdU+/vWF+ cells expressing in hippocampus. Furthermore, the level of choline acetyltransferase (ChAT) was considerably enhanced and Aβ deposition was decreased in the brains of mice upon VEGF treatment. These observations suggest that VEGF should be pursued as a novel therapeutic agent for treatment of AD. [Copyright &y& Elsevier]