No abstract

MicroRNAs play an important role in tumor development and progression. Tumor growth is closely associated with glucose metabolism. Specifically, tumor cells produce energy (ATP) under aerobic and anaerobic conditions through glycolysis and metabolites, such as lactic acid and ATP, as a result of the Warburg effect. However, the transport of glucose into cells depends on protein transporters in the cell membrane. Therefore, this area has recently become a topic of interest for research on targeted cancer therapy. We found that miRNA-451 inhibits the phosphatidylinositol-3 kinase (PI3K)/Akt signaling pathway to modify the biological behavior of glioma cells. Inhibiting the PI3K/Akt pathway may prevent glucose-addicted cancer cells from performing glycolysis. Akt directly affects glycolysis by regulating the localization of the glucose transporter 1 (GLUT1). However, how miRNA-451 regulates glucose transporters on the cell membrane and affects the regulatory mechanisms of glucose metabolism in glioma cells remains unclear. Consequently, we predict and verify related gene protein interactions. By targeting CAB 39, miRNA-451 likely triggers the LKB1/AMPK/PI3K/AKT pathway, which regulates GLUT1, to inhibit the glucose metabolism of, reduce the energy supply to, and inhibit the proliferation and invasion of glioma cells. Our results suggest a new direction for the treatment of glioma.

Aberrant expressions of long noncoding RNAs (lncRNAs) contribute to carcinogenesis via regulating tumor suppressors or oncogenes. LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been recognized as an oncogene to promote tumor progression of many cancers. However, the function of NEAT1 in glioma remains poorly discovered. Currently, we focused on the role of NEAT1 in glioma. Here, we found that NEAT1 was greatly upregulated in glioma cells compared with normal human astrocytes (NHAs). Meanwhile, miR‐107 was significantly downregulated in glioma cell lines. Then, we observed that knockdown of NEAT1 suppressed the growth and invasion of glioma cells including U251 and SW1783 cells. Reversely, overexpression of NEAT1 dramatically induced glioma cell survival, increased cell colony formation, and promoted cell invasion ability. Subsequently, bioinformatics analysis was performed to predict the correlation between NEAT1 and miR‐107. Moreover, it was revealed that NEAT1 could modulate miR‐107 via serving as an endogenous sponge of miR‐107. The direct binding correlation between NEAT1 and miR‐107 was validated in our study. In addition, cyclin dependent kinase 14 (CDK14) was predicted as an messenger RNA target of miR‐107 and the association between them was confirmed in our research. Moreover, we implied that NEAT1 demonstrated its biological functions via regulating miR‐107 and CDK14 in vivo. In summary, our findings indicated that NEAT1/miR‐107/CDK14 axis participated in glioma development. NEAT1 could act as a significant prognostic biomarker in glioma progression.

Traumatic brain injury (TBI) has emerged as a leading cause of mortality and morbidity worldwide. Transplantation of bone mesenchymal stem cells (BMSCs) has emerged as a promising treatment for various central nervous system diseases. This study aims to evaluate the effect of BMSCs transplantation by intravenous injection on neurological function and angiogenesis of the TBI mice. C57BL/6 male mice were randomly divided into four groups: control, sham, TBI, and BMSC. Functional neurological evaluation was performed 1, 4, 7, 14, and 21 days after TBI using neurological severity scores. The impairment of learning and memory in mice was evaluated 14 days after TBI by Morris water maze experiment. Mice were sacrificed 14 days after TBI, and then brain sections were stained by terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick end labeling staining to assess brain neuronal apoptosis. Immunohistochemistry was conducted to evaluate caspase-3 activity and identify vascular distribution and microvessel density. Protein and mRNA levels of vascular endothelial growth factor (VEGF) and angiogenin-1 (Ang-1) in brain tissues were analyzed by Western blot and quantitative real-time polymerase chain reaction, respectively. BMSCs transplantation promoted recovery of neurological function, ameliorated impairment of learning and memory, attenuated neuronal apoptosis, and diminished caspase-3 activation in mice after TBI. Also, BMSCs transplantation upregulated expressions of VEGF and Ang-1 and promoted the formation of microvessels in brain tissues after TBI. Our study demonstrated the important role of BMSCs transplantation in TBI mouse and indicated that the underlying mechanism was through promoting angiogenesis and improving neurological function. This provides a novel and effective strategy for cell-based therapy in the treatment of TBI.

To investigate the function of microRNA-31 (miR-31) in the pathogenesis of gastric cancer (GC) and to explore the possible mechanisms involved in it. A quantitative real-time reverse transcription-PCR (RT-PCR) analysis was performed to evaluate miR-31 expression in GC cell lines. After transfecting GC cells with miR-31 precursors, Alamar blue and apoptosis assays were used to measure the respective proliferation and apoptosis rates. SGPP2 and Smad4 expression were determined by real-time RT-PCR and western blot assays after miR-31 transfection. Animal assay was used to further investigate miR-31 in the pathogenesis of GC. miR-31 was significantly reduced in GC tissues and GC cell lines, and that the reduced miR-31 was associated with distant metastasis and GC clinical pathological stages, miR-31 was lower at stages III/IV than that at stage II. SGPP2 and Smad4 were proven to be the direct target of miR-31. SGPP2 and Smad4 at mRNA and protein levels were negatively correlated with miR-31 in human GC tissues and cancer cell lines. Increased miR-31 significantly repressed SGPP2 and Smad4 at transcriptional and translational levels. Functional studies showed that increasing miR-31 inhibited GC cell proliferation, promoted apoptosis and attenuated cell migration, which were also linked to downregulation of STAT3. In vivo, miR-31 inhibited GC cell growth in tumor-bearing mice. This study has revealed miR-31 as a tumor suppressor and has identified SGPP2 and Smad4 as novel targets of miR-31, linking to STAT3 for regulating cancer cell proliferation, apoptosis and migration in GC. Therefore, miR-31 could be a useful biomarker for monitoring GC development and progression, and also could have a therapeutic potential by targeting SGPP2, Smad4 and STAT3 for GC therapy.