LncRNA MEG3在胃癌中的表达及其与糖酵解相关性的研究

Study on Expression of LncRNA MEG3 in Gastric Cancer and its Correlation With Glycolysis

背景:糖代谢异常是肿瘤的恶性特征之一,Lnc RNA在肿瘤有氧糖酵解过程中发挥重要作用。目的:探讨Lnc RNA MEG3在胃癌组织中的表达及其与胃癌糖酵解之间的相关性。方法:应用RT-q PCR法检测胃癌和癌旁组织中MEG3 m RNA表达,免疫组化En Vision法检测胃癌和癌旁组织中PKM2、LDHA、m TOR、HIF-1α蛋白表达,并分析其与胃癌临床病理特征的关系。采用Spearman相关性分析评估MEG3与胃癌糖酵解水平的相关性,并初步探讨其作用机制。结果:胃癌组织中MEG3表达明显低于癌旁组织(P<0.05),并与淋巴结转移有关(P<0.05);PKM2、LDHA、m TOR、HIF-1α的阳性表达率均明显高于癌旁组织(P<0.05),并与肿瘤浸润深度、淋巴结转移、p TNM分期等相关(P<0.05)。Spearman相关性分析示MEG3与PKM2、LDHA、m TOR、HIF-1α表达均呈负相关(r=-0.346,r=-0.306,r=-0.389,r=-0.338;P<0.05)。HIF-1α+/m TOR+组中MEG3表达明显低于HIF-1α-/m TOR-组,而PKM2、LDHA阳性表达率均明显高于HIF-1α-/m TOR-组(P<0.05)。生存分析表明PKM2、LDHA、m TOR表达与胃癌患者生存密切相关,与阴性表达组相比,阳性表达组患者的生存时间显著缩短(P<0.05)。Cox多因素回归分析显示PKM2是胃癌患者预后的独立危险因素(P<0.05)。结论:Lnc RNA MEG3在胃癌组织中低表达,与糖酵解水平呈负相关;MEG3可能通过对m TOR、HIF-1α的负向调节抑制胃癌糖酵解,从而在胃癌进展中发挥抑癌作用。

Background:Abnormal glucose metabolism is one of the malignant characteristics of tumors.LncRNA plays an important role in the process of aerobic glycolysis of tumors.Aims:To investigate the expression of LncRNA MEG3 in gastric cancer and its correlation with glycolysis.Methods:RT⁃qPCR was used to detect the mRNA expression of MEG3 in gastric cancer and paracancerous tissue.Immunohistochemical EnVision method was used to detect the protein expressions of PKM2,LDHA,mTOR,HIF⁃1αin gastric cancer and paracancerous tissue.Relationship between expressions of above⁃mentioned indices and clinicopathological features of gastric cancer were analyzed.The correlation between MEG3 and glycolysis level of gastric cancer was analyzed by Spearman correlation analysis,and its possible mechanism was explored.Results:The expression of MEG3 in gastric cancer tissue was significantly lower than that in paracancerous tissue(P<0.05),and was correlated with lymph node metastasis(P<0.05).The positivity rates of expression of PKM2,LDHA,mTOR and HIF⁃1αin gastric cancer tissue were significantly higher than those in paracancerous tissue,and were correlated with the depth of tumor invasion,lymph node metastasis and pTNM stage(P<0.05).Spearman correlation analysis showed that the expression of MEG3 was negatively correlated with the expressions of PKM2,LDHA,mTOR and HIF⁃1α(r=-0.346,r=-0.306,r=-0.389,r=-0.338;P<0.05).The expression of MEG3 in HIF⁃1α+/mTOR+group was significantly lower than that in HIF⁃1α-/mTOR-group,while the positivity rates of expression of PKM2,LDHA were significantly higher than those in HIF⁃1α-/mTOR-group(P<0.05).Survival analysis showed that the expressions of PKM2,LDHA and mTOR were closely related to the survival of gastric cancer patients,and the survival time of patients with positive expression was significantly reduced compared with negative expression group(P<0.05).Cox risk regression analysis showed that PKM2 was an independent risk factor for the prognosis of gastric cancer(P<0.05).Conclusions:LncRNA MEG3 is down⁃regulated in gastric cancer tissue and negatively correlated with the level of glycolysis.MEG3 may play an inhibitory role in the progression of gastric cancer by inhibiting glycolysis through negative regulation of mTOR and HIF⁃1α.