miR-9-5p通过靶向UBE4B调节缺氧诱导转录因子1α泛素化介导瓦博格效应在胶质瘤细胞中的应用

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Abstract Objective To explore the regulation and mechanism of miR-9-5p on Waburg effect in glioma. Methods Thirty patient’s glioma and paracancerous tissue samples diagnosed from May 2018 to October 2020 in the Second Affiliated Hospital of Xinjiang Medical University were selected. A control group, a miR-9-5p overexpression group, and a miR-9-5p inhibitor group were established. Quantitative real-time PCR was used to detect the expression of miR-9-5p and its correlation with the expression of glycolysis-related genes. Construction of ectopic tumor models and in vitro cell experiments, using quantitative real-time PCR, Western blot, glucose uptake analysis, lactic acid production detection and cell viability detection to determine the impact of miR-9-5p on glioma and Warburg effect, while the dual luciferase reporter gene was used to detect the targeting relationship between miR-9-5p and UBE4B. Results The expressions of Hypoxia inducible factor-1α(HIF1α) protein, glucose transporter 1 (Glut1), human hexokinase-2 (HK2), lactate dehydrogenase (LDHA) and vascular endothelial growth factor (VEGF) in the miR-9-5p overexpression group were significantly higher than those in the control group, and the differences were statistically significant (P ＜ 0.05); while the mRNA level of HIF1α was not statistically significant (P ＞ 0.05). The expressions of HIF1α protein, Glut1, HK2, LDHA and VEGF in the miR-9-5p inhibitor group were significantly lower than those in the control group, and the differences were statistically significant (P ＜ 0.05); while the mRNA levels of HIF1α were not statistically significant (P ＞ 0.05). Compared with the control group, the miR-9-5p overexpression group significantly enhanced metabolism and metastasis (P ＜ 0.05), while the miR-9-5p inhibitor group significantly reduced glucose uptake and lactate production in U251 cells (P < 0.05). The cell viability of the miR-9-5p overexpression group was significantly higher than that of the control group after treatment for 24 h and 48 h, and the differences were statistically significant (P ＜ 0.05); compared with the control group, the cell viability of the miR-9-5p inhibitor group decreased significantly at 24 h and 48 h, and the differences were statistically significant (P ＜ 0.05). The tumor volume and wet weight of the miR-9-5p overexpression group were significantly higher than those of the control group, and the differences were statistically significant (P ＜ 0.05). The protein level of UBE4B in the miR-9-5p overexpression group was lower than that in the control group, and the difference was statistically significant (P < 0.05); the expression of HIF1α and glycolysis-related genes (Glut1, HK2 and LDHA) was significantly higher than that of the control group, and the difference was statistically significant (P ＜ 0.05). Conclusion miR-9-5p can regulate the Warburg effect of gliomas and promote the occurrence and development of gliomas through the UBE4B/HIF1α pathway.

Key words： UBE4B Hypoxia inducible factor-1α miR-9-5p Glioma Warburg effect

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	ZHANG Jingjing YALIKUN Nu’er’aihemaitijiang DU Peng

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ZHANG Jingjing YALIKUN Nu’er’aihemaitijiang DU Peng. Application of miR-9-5p in targeting UBE4B in regulating hypoxia-induced transcription factor 1α ubiquitination-mediated Warburg effect in glioma cells[J]. 中国医药导报, 2021, 18(22): 28-32，36.

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https://www.yiyaodaobao.com.cn/EN/ OR https://www.yiyaodaobao.com.cn/EN/Y2021/V18/I22/28

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