MicroRNA-140-5p is Downregulated in Osteosarcoma and Overexpression of MicroRNA-140-5p Inhibits Cancer Cell Proliferation by Downregulating GLUT-1.

BACKGROUND: MicroRNA-140-5p plays pivotal role in different types of human malignancies, while its involvement in osteosarcoma is unknown. OBJECTIVE: Our study aimed to investigate the functionality of microRNA-140-5p in osteosarcoma. METHODS: Plasma levels of microRNA-140-5p and glucose transporter 1 (GLUT-1) in both osteosarcoma and healthy controls were measured by qRT-PCR and ELISA, respectively. Correlation between plasma levels of microRNA-140-5p and GLUT-1 was analyzed by Pearson correlation coefficient. Correlation between plasma levels of microRNA-140-5p and clinical data of patients with osteosarcoma was analyzed by Chi-square test. MicroRNA-140-5p mimic and GLUT-1 expression vector were transfected into cells of human osteosarcoma cell lines, and the effects on microRNA-140-5p expression, GLUT-1 expression and cell proliferation were analyzed by qRT-PCR, Western-blot and CCK-8 assay, respectively. RESULTS: Plasma levels of microRNA-140-5p were significantly lower and plasma levels of GLUT-1 were significantly higher in osteosarcoma patients than that in healthy controls. Levels of plasma microRNA-140-5p and GLUT-1 were reversely correlated in osteosarcoma patients. Plasma levels of microRNA-140-5p were correlated with tumor size but not with other clinical data of patients. MicroRNA-140-5p mimic significantly inhibited cancer cell proliferation, while GLUT-1 overexpression significantly promoted cancer cell proliferation. MicroRNA-140-5p mimic significantly downregulated GLUT-1 expression. CONCLUSION: GLUT-1 overexpression showed no significant effect on microRNA-140-5p expression but attenuated the inhibitory effects of microRNA-140-5p mimic on cell proliferation. We therefore conclude that microRNA-140-5p is downregulated in osteosarcoma and overexpression of microRNA-140-5p may inhibit cancer cell proliferation by downregulating GLUT-1.

LRCH1 polymorphisms linked to delayed encephalopathy after acute carbon monoxide poisoning identified by GWAS analysis followed by Sequenom MassARRAY® validation.

BACKGROUND: We explored the association of leucine-rich repeats and calponin homology domain containing 1 (LRCH1) gene polymorphisms with genetic susceptibility to delayed encephalopathy after acute carbon monoxide poisoning (DEACMP), which might provide a theoretical basis for the pathogenesis, diagnosis, and prognosis research of DEACMP. METHODS: Four single nucleotide polymorphisms, rs1539177 (G/A), rs17068697 (G/A), rs9534475 (A/C), and rs2236592 (T/C), of LRCH1, selected as candidate genes through genome-wide association analysis, were genotyped in 661 patients (DEACMP group: 235 cases; ACMP group: 426 cases) using Sequenom Massarray®. The association analysis of four SNPs and LRCH1 was performed under different genetic models. RESULTS: LRCH1 polymorphisms (rs1539177, rs17068697, rs9534475) under additive and dominant genetic models were significantly associated with an increased risk of DEACMP, but no significant association under allele and recessive models was found. The LRCH1 rs2236592 polymorphism was susceptible to DEACMP only under the dominant model (TT/TC + CC, OR = 1.616, 95% CI: 1.092-2.390, P = 0.015784). In addition, the A allele gene of rs9534475 polymorphism in LRCH1 might increase the risk for DEACMP (OR = 1.273, 95% CI: 1.013-1.601, P = 0.038445). CONCLUSIONS: We found a significant association between the four LRCH1 polymorphisms and DEACMP. The allelic A of rs9534475 polymorphism in LRCH1 might be a risk factor for DEACMP.

Curcumin Promotes Proliferation of Adult Neural Stem Cells and the Birth of Neurons in Alzheimer's Disease Mice via Notch Signaling Pathway.

The abnormal deposition of amyloid-ß peptide, a major component of senile plaques, has been reported to be the major cause of neuronal cell death and cognitive impairment in Alzheimer's disease (AD). Adult neurogenesis is related to the amelioration of impaired neurons and cognitive impairment. In the research, we investigated the function of curcumin on endogenous neural stem cells (NSCs) and hippocampal neurogenesis in mice. APP/PS1 transgenic mice as animal models were treated with curcumin, and a significant improvement in learning and memory function was observed. The improvement was associated with a significant increase in the number of new neural stem cells (BrdU+/Nestin+) and newborn neurons (NeuN/kI67+) in the hippocampal region and decreased the number of apoptotic neurons (TUNEL+ and Caspase-3/NeuN+). These results suggested that curcumin activated NSCs proliferation, improved neurogenesis, and ameliorated cognitive impairment of AD mice. Then, we identified that curcumin upregulated the expression of self-renewal genes, Notch1 and Hes1, and augmentation of CDK4, Cyclin D1, NICD, and Hes1 protein. As Notch activity was blocked by the DAPT, the related proteins were downregulated, and the initiating cell proliferation of curcumin was abolished. These results might suggest that the function of curcumin was dependent on Notch signaling pathway.