LncRNA ZFPM2-AS1对肝细胞癌的预后影响及机制研究

Prognostic effect and mechanism of LncRNA ZFPM2-AS1 on hepatocellular carcinoma

目的分析LncRNA ZFPM2反义RNA1(ZFPM2 antisense RNA1,ZFPM2-AS1)对肝细胞癌预后的影响及其潜在的致病机制。方法采用癌症基因组图谱(The cancer genome atlas,TCGA)数据库相关基因表达谱并结合临床病理学指标综合分析ZFPM2-AS1对肝细胞癌诊断及预后的效能及其与临床病理学指标的相关性;通过siRNA干扰ZFPM2-AS1的表达,采用5-乙炔基-2’脱氧尿嘧啶核苷染色(EdU)法检测HepG2细胞增殖活力、Transwell实验检测细胞迁移和侵袭能力、免疫印迹法检测下游蛋白质表达水平的变化;通过GO和KEGG分析,初步探究ZFPM2-AS1调控肝细胞癌进程的潜在机制。结果ZFPM2-AS1在肝细胞癌组织中显著高表达(P<0.01),影响患者的生存时间(P<0.001),且与年龄(P=0.004)、T分期(P=0.011)、临床分期(P=0.033)及甲胎蛋白水平(P=0.050)密切相关。ZFPM2-AS1可促进HepG2细胞的增殖、迁移及侵袭能力,抑制B淋巴细胞瘤-2蛋白相关蛋白(BAX)、E-钙黏蛋白(E-cadherin)的表达,增强B淋巴细胞瘤-2蛋白(BCL2)、细胞周期蛋白D1(cy-clin D1)、N-钙黏蛋白(N-cadherin)的表达。GO和KEGG分析显示,ZFPM2-AS1可能与烟酰胺腺嘌呤二核苷酸磷酸(NADP)代谢过程、戊糖代谢过程、NADP结合以及氧化还原酶活性等生物学功能有关,同时与碳代谢、磷酸戊糖途径和谷胱甘肽代谢等通路密切相关。结论ZFPM2-AS1促进肝细胞癌的增殖、迁移和侵袭并参与肝细胞癌的发生、发展。

Objective To investigate the impact of LncRNA ZFPM2-AS1 on hepatocellular cancer prognosis and its probable pathogenic mechanism.Methods The TCGA database-related gene expression profiles were employed in conjuncion with a complete analysis of clinicopathological indicators to assess the efficacy of ZFPM2-AS1 in the diagnosis and prognosis of hepatocellular carcinoma,as well as its correlation with clinicopathological indicators.The expression of ZFPM2-AS1 was interfered by siRNA,the proliferation activity of HepG2 cells was detected by 5-ethyney-2'deoxyuracil nucleoside staining(EdU),the migration and invasion ability of HepG2 cells was detected by Transwell assay,and the changes of downstream protein expression level were detected by western blot.GO and KEGG analysis were performed to investigate ZFPM2-potential mechanisms of AS1 regulation of hepatocellular carcinoma progression.Results ZFPM2-AS1 was found as strongly expressed in hepatocellular carcinoma tissues(P<0.01),affecting patient survival time(P<0.001),and it was shown as significantly connected with age(P=0.004),T stage(P=0.011),and clinical stage(P=0.033)and alpha-fetoprotein level(P=0.050)were shown as significantly associated.ZFPM2-AS1 can stimulate HepG2 cell proliferation,migration,and invasion while inhibiting BAX and E-cadherin expression and increasing BCL2,cyclin D1,and N-cadherin expression.ZFPM2-AS1 may be connected to biological functions,such as NADP metabolism,pentose metabolism,NADP binding,and oxidoreductase activity,and it is strongly associated to carbon metabolism,pentose phosphate pathway and glutathione metabolism,according to GO and KEGG analysis.Conclusion ZFPM2-AS1 enhances hepatocellular carcinoma proliferation,migration,and invasion,as well as its occurrence and progression.