Fructose-1,6-bisphosphatase 2 represses cervical cancer progression via inhibiting aerobic glycolysis through promoting pyruvate kinase isozyme type M2 ubiquitination.

Growing evidence has shown that aerobic glycolysis, as a hallmark of cancer cells, plays a crucial role in cervical cancer. The aim of the study is to uncover whether fructose-1,6-bisphosphatase 2 (FBP2) is involved in cervical cancer progression via the aerobic glycolysis pathway. FBP2 levels were determined by quantitative PCR (qPCR) and western blotting. Cell growth viability and apoptosis were tested by cell counting kit-8 (CCK-8) and flow cytometry assays. Immunoprecipitation assay was applied for the detection of the FBP2 effect on pyruvate kinase isozyme type M2 (PKM2) ubiquitination. FBP2 level was decreased in cervical cancer, which is closely linked to shorter overall survival. FBP2 decreased cell growth and aerobic glycolysis and increased cell apoptosis, as well as decreased PKM2 expression and increased its ubiquitination level. The above-mentioned roles of FBP2 were weakened followed by PKM2 overexpression. FBP2 inhibited cervical cancer cell growth via inhibiting aerobic glycolysis by inducing PKM2 ubiquitination.

LncRNA UCA1 facilitated cell growth and invasion through the miR-206/CLOCK axis in glioma.

BACKGROUND: Glioma is a lethal malignant brain tumor, which affects the brain functions and is life-threatening. LncRNA UCA1 was identified as a pivotal regulator for tumorigenesis of glioma. MiR-206 was discovered to promote tumorigenesis and is critical in the regulation of cell proliferation in glioma. This study will discuss the expression of UCA1 regarding miR-206 and CLOCK, and their integrative effects in the proliferation and cell cycle of glioma cells. METHODS: qRT-PCR was conducted to measure the mRNA expressions of IgG and Ago2 in cells co-transfected with UCA1, and miR-216 in U251. Bioinformation was analyzed for the prediction of association between UCA1 and miR-206. Transwell migrations assays and invasion assays were utilized to observe the cell invasive ability. Western blot and immunofluorescence imaging were used to examine the protein expressions. In vivo comparisons and observations were also performed to investigate the role of UCA1 in glioma growth. RESULTS: LncRNA UCA1 was up-regulated in glioma cell lines and tissues. It elevated cell invasion via the inducing of epithelial-mesenchymal transition. We found that UCA1 can modulate miR-206 expression and serve as an endogenous sponge of miR-206. The EMT-inducer CLOCK was validated as a messenger RNA target of miR-206. At last, we demonstrated that UCA1 exerted the biology function through regulating miR-206 and CLOCK in vivo. CONCLUSIONS: Overall, the results demonstrated that UCA1/miR-206/CLOCK axis participated in the progressing of glioma and could act as a promising therapeutic target.

Intracarotid cold saline infusion contributes to neuroprotection in MCAO­induced ischemic stroke in rats via serum and glucocorticoid­regulated kinase 1.

Intracarotid cold saline infusion (ICSI) brings about neuroprotective effects in ischemic stroke. However, the involvement of serum and glucocorticoid­regulated kinase 1 (SGK1) in the underlying mechanism of ICSI is not fully understood; therefore, we used the rat middle cerebral artery occlusion (MCAO) model to investigate the neuroprotective effects of ICSI on ischemic stroke in rats, as well as the involvement of SGK1 in these effects. ICSI decreased infarct size and brain swelling, as determined by 2,3,5­triphenyltetrazolium chloride staining and the dry­wet weight method, respectively. The results of terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) and Nissl staining showed that ICSI also suppressed apoptosis and increased the relative integral optical density (IOD) values of Nissl bodies in the rat MCAO model. Regarding the mechanism, the results of immunohistochemistry and western blotting revealed that ICSI upregulated SGK1 expression and downregulated beclin­1 and LC­3 expression in the rat MCAO model. In addition, SGK1 knockdown increased ICSI­mediated infarct size and brain swelling, promoted apoptosis, and reduced the IOD values of Nissl bodies in the rat MCAO model. In addition, we found that SGK1 knockdown upregulated beclin­1 and LC­3 expression mediated by ICSI. Overall, ICSI had a neuroprotective effect on ischemic stroke after reperfusion by upregulating SGK1 and inhibiting autophagy.