LncRNA SNHG15 promotes the proliferation of nasopharyngeal carcinoma via sponging miR-141-3p to upregulate KLF9.

OBJECTIVE: Long non-coding RNAs (lncRNAs) have been identified to exert an oncogenic or anti-tumor function in malignant tumors. LncRNA SNHG15 is verified to be an oncogene in hepatocellular carcinoma, colorectal cancer, and prostate cancer. In this paper, we mainly investigate the potential influence of SNHG15 on the progression of nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: SNHG15 levels in NPC tissues and cell lines were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Correlation between SNHG15 level and prognosis of NPC patients was evaluated by the Kaplan-Meier method. Regulatory effects of SNHG15 on proliferative, colony formation abilities, and apoptosis of SUNE1 and CNE1 cells were assessed through a series of functional experiments. Potential miRNAs binding SNHG15 and the downstream gene of the microRNA (miRNA) were predicted by bioinformatics method, which was confirmed by Dual-Luciferase reporter gene assay and Western blot. RESULTS: SNHG15 was upregulated in NPC tissues and cells. High level of SNHG15 indicated worse survival in NPC patients. Knockdown of SNHG15 markedly suppressed proliferative ability and induced apoptosis in SUNE1 and CNE1 cells. It is verified that miR-141-3p was the direct target binding SNHG15, and KLF9 was the downstream gene of miR-141-3p. SNHG15 was demonstrated to be a ceRNA to upregulate KLF9 by competitively binding miR-141-3p. CONCLUSIONS: SNHG15 is upregulated in NPC tissues, and this aggravates the progression of NPC by absorbing miR-141-3p to upregulate KLF9.

Metabolic effects of 4-pentenoate on isolated dog kidney tubules.

The effects of 4-pentenoate (0.01 to 10 mM) were studied on suspensions of cortical tubules and of thick ascending limbs (TAL) prepared from dog kidneys. When cortical tubules were incubated with 1 mM glutamine, 4-pentenoate accelerated glutamine uptake, ammoniagenesis, and the production of alpha-ketoglutarate, lactate and pyruvate, but decreased gluconeogenesis. With 5 mM glutamine, the marked accumulation of alpha-ketoglutarate reversed the net fluxes through the alanine and aspartate aminotransferases. When cortical tubules or TAL were incubated with lactate, its utilization and gluconeogenesis (in cortical tubules) were markedly decreased by 4-pentenoate. The mitochondrial NAD+/NADH ratio was markedly increased by 4-pentenoate in cortical tubules but not in TAL. The production of 14CO2 from 14C[1]-pyruvate or 14C-[1]-alpha-ketoglutarate was decreased by approximately 60% by 4-pentenoate in cortical tubules but not in TAL. In cortical tubules, these findings are best explained by depletion of mitochondrial free CoA, inhibition of pyruvate and alpha-ketoglutarate dehydrogenases and decreased mitochondrial NADH. By contrast, in TAL, accumulation of reducing equivalents probably resulted from the metabolism of 4-pentenoate itself.

Experimental Fanconi's syndrome resulting from 4-pentenoate infusion in the dog.

Studies were performed in anesthetized dogs to evaluate the effects of 4-pentenoate on urinary electrolyte excretion and renal metabolism. The intravenous administration of 4-pentenoate (1 mumol.kg-1.min-1 during 180 min) markedly increased the urinary excretion of bicarbonate, phosphate, potassium, amino acids, glucose, and various organic anions, whereas that of sodium and chloride also rose but less strikingly. These results suggest that 4-pentenoate markedly inhibits the proximal reabsorption of various solutes and therefore reproduces an experimental Fanconi's syndrome. Despite the rise in renal cortical concentration of alpha-ketoglutarate, glutamine utilization and total ammonia production expressed per 100 ml glomerular filtration rate increased following 4-pentenoate infusion, the ammonia being diverted into the renal vein. This increment in glutamine utilization was equal to the combined rise in the renal production of glutamate and alpha-ketoglutarate. By contrast, renal lactate utilization was drastically reduced. A causal relationship between the decreased renal cortical ATP concentration and the inhibited reabsorption of various solutes is suggested but cannot be established unequivocally.

Enzymatic basis of renal adaptation to acidosis in the dog.

The effect of pH on the activities of various enzymes along the ammoniagenic pathway was tested on dog kidney cortex homogenates in an attempt to identify the metabolic steps that could be directly influenced by a low pH in this species. The activity of alphaketoglutarate dehydrogenase was markedly stimulated by acidification of the medium that decreased abruptly the km for alphaketoglutarate. By contrast, succinyl CoA synthetase and malate dehydrogenase remained relatively insensitive to pH changes. The apparent km of malic enzyme for malate was markedly decreased by an acid medium. Therefore these findings suggest that an acid pH regulates the ammoniagenic pathway at two critical sites: alphaketoglutarate dehydrogenase and malic enzyme. These stimulated enzymatic activities may account for the changes in renal cortical concentrations of metabolites observed during metabolic or respiratory acidosis.