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  • Author or Editor: Huiming Yu x
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Fengming Lan, Qing Qin, Huiming Yu and Xiao Yue

OBJECTIVE

Although glucose metabolism reengineering is a typical feature of various tumors, including glioma, key regulators of glycolytic reprogramming are still poorly understood. The authors sought to investigate whether glycolysis inhibition by microRNA (miR)–448 increases radiosensitivity in glioma cells.

METHODS

The authors used glioma tissue samples from glioma patients, cells from glioblastoma (GBM) cell lines and normal human astrocyte cells, and subcutaneous tumor–bearing U87 cells in mice to examine the effects of signaling regulation by miR-448 in the response of glioma tissues and cells to radiation treatment. Techniques used for investigation included bioinformatics analyses, biochemical assays, luciferase reporter assays, and establishment of subcutaneous tumors in a mouse model. Glucose consumption, LDH activity, and cellular ATP were measured to determine the ability of glioma cells to perform glycolysis. Expression of HIF-1α was measured as a potential target gene of miR-448 in glycolysis.

RESULTS

miR-448 was detected and determined to be significantly downregulated in both glioma tissues from glioma patients and GBM cell lines. Furthermore, miR-448 acted as a tumor-inhibiting factor and suppressed glycolysis in glioma by negatively regulating the activity of HIF-1α signaling and then interfering with its downstream regulators relative to glycolysis, HK1, HK2, and LDHA. Interestingly, overexpression of miR-448 increased the x-radiation sensitivity of glioma cells. Finally, in in vivo experiments, subcutaneous tumor–bearing U87 cells in a mouse model verified that high expression of miR-448 also enhanced glioma radiosensitivity via inhibiting glycolytic factors.

CONCLUSIONS

miR-448 can promote radiosensitivity by inhibiting HIF-1α signaling and then negatively controlling the glycolysis process in glioma. A newly identified miR-448–HIF-1α axis acts as a potentially valuable therapeutic target that may be useful in overcoming radioresistance in glioma treatment.

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Ming-liang Yang, Jian-jun Li, Shao-cheng Zhang, Liang-jie Du, Feng Gao, Jun Li, Yu-ming Wang, Hui-ming Gong and Liang Cheng

The authors report a case of functional improvement of the paralyzed diaphragm in high cervical quadriplegia via phrenic nerve neurotization using a functional spinal accessory nerve. Complete spinal cord injury at the C-2 level was diagnosed in a 44-year-old man. Left diaphragm activity was decreased, and the right diaphragm was completely paralyzed. When the level of metabolism or activity (for example, fever, sitting, or speech) slightly increased, dyspnea occurred. The patient underwent neurotization of the right phrenic nerve with the trapezius branch of the right spinal accessory nerve at 11 months postinjury. Four weeks after surgery, training of the synchronous activities of the trapezius muscle and inspiration was conducted. Six months after surgery, motion was observed in the previously paralyzed right diaphragm. The lung function evaluation indicated improvements in vital capacity and tidal volume. This patient was able to sit in a wheelchair and conduct outdoor activities without assisted ventilation 12 months after surgery.