SMYD2在宫颈癌中的表达变化及意义

Expression changes and its significance of SMYD2 in cervical cancer

摘要:

目的 探讨组蛋白赖氨酸甲基转移酶SET和MYND结构域蛋白2（SET and MYND domain-containing protein 2，SMYD2）在宫颈癌细胞糖代谢中的作用，进一步研究其是否与宫颈癌增殖有关。方法 通过基因表达谱交互分析（gene expression profiling interactive analysis，GEPIA）数据库分析SMYD家族成员在宫颈癌中的表达和预后价值，通过log-rank检验进行生存差异比较。通过SMYD2的shRNA敲低或过表达技术来研究SMYD2在宫颈癌中的糖代谢作用。结果 宫颈癌组织中SMYD2的表达与患者年龄、性别、肿瘤组织分化程度无关，SMYD2的过表达预示总体生存期较差与临床分期相关（F=4.520，P=0.004）。生物信息分析揭示了SMYD2在调控宫颈癌中Warburg效应中发挥调节作用。通过功能缺失实验，证明SMYD2的敲低抑制了宫颈癌细胞的有氧糖酵解，表现为葡萄糖摄取减少，乳酸生成降低和细胞外酸化减弱，而SMYD2过表达则促进子宫颈癌细胞的糖酵解代谢。此外，SMYD2是宫颈癌细胞生长所必需的，并且这种致癌作用主要依赖糖酵解。结论 SMYD2在宫颈癌细胞中过表达并在肿瘤代谢中发挥重要作用，能够通过调节有氧酵解促进宫颈癌细胞增殖。

Abstract:

Objective To explore the role of SET and MYND domain-containing protein 2（SMYD2） in the glucose metabolism of cervical cancer cell，and further study whether it is related to cervical cancer proliferation.Methods Gene expression profiling interactive analysis（GEPIA） was used to analyze the expression profile and prognosis of SMYD family members in cervical cancer，and survival differences were compared by log-rank test. The role of SMYD2 in glucose metabolism in cervical cancer was studied by shRNA knockdown or overexpression of SMYD2.Results The expression of SMYD2 in cervical cancer tissues was not related to age，gender and the degree of tissue differentiation，but was related to clinical stage（F=4.520， P=0.004）. The high expression of SMYD2 predicted poor overall survival. Bioinformatics analysis revealed that SMYD2 played a regulatory role in regulating the Warburg effect in cervical cancer. The deletion of SMYD2 inhibited aerobic glycolysis of cervical cancer cells by functional loss experiments，which showed decreased glucose uptake，lactic acid production and extracellular acidification. SMYD2 overexpression promotes glycolysis metabolism of cervical cancer cells. In addition， SMYD2 was essential for the growth of cervical cancer cells， and this carcinogenic activity was mainly dependent on glycolysis.Conclusion SMYD2 is overexpressed in cervical cancer cells and plays an important role in tumor metabolism， which can promote the proliferation of cervical cancer cells by regulating aerobic glycolysis.