Lnc MALAT1介导OLA1在肝细胞癌中表达及分子机制

Lnc MALAT1 mediated expression and molecular mechanism of OLA1 in hepatocellular carcinoma

目的:探究Obg样ATP酶1(OLA1)及相关非编码RNA(ncRNAs)在肝细胞癌发生发展中的作用及分子机制。方法:利用Oncomine和TCGA数据库分析OLA1基因在肝细胞癌和正常样本中的表达情况。利用GEPIA和Kaplan-Meier Plotter数据库分析OLA1基因与肝细胞癌临床病理特征和预后的关系。利用starBase数据库预测并筛选OLA1上游miRNA并分析miRNA(miR-144-3p)在肝细胞癌中表达水平。利用starBase和GEPIA数据库预测miRNA(miR-144-3p)上游相关lncRNA,分析其在肝细胞癌中表达和生存情况。结果:OLA1基因在肝细胞癌样本中表达水平显著高于正常样本,且与肝细胞癌患者总生存期呈负相关(P<0.01)。肝细胞癌组织中OLA1基因表达水平与肝细胞癌的TNM分期、肿瘤分化程度及血管侵犯和不良预后存在显著相关性(P<0.01)。相关性分析发现肝细胞癌中lncRNA MALAT1与miR-144-3p负相关,且与OLA1基因显著正相关(P<0.01)。结论:OLA1基因的表达水平可作为支持肝细胞癌诊断和彰显其预后的潜在标志物,MALAT1-miR-144-3p轴对该基因的表达发挥着调控作用。

Objective To investigate whether the ncRNAs-mediated expression of Obg-like ATPase1(OLA1)gene correlates with clinical significance and molecular mechanism in hepatocellular carcinoma. Methods The Oncomine and TCGA database were used to analyze the expression of OLA 1 gene in HCC. The GEPIA and Kaplan-Meier Plotter databases were used to analyze the relationship between OLA1 gene and clinicopathological features and prognosis of hepatocellular carcinoma. The starBase database was used to predict and screen the upstream miRNA of OLA1 gene and analyze the expression level of miRNA(miR-144-3p) in hepatocellular carcinoma. Upstream lncRNAs of miRNA(miR-144-3p) were predicted, using StarBase and GEPIA databases.Results OLA1 mRNA was highly expressed in hepatocellular carcinoma tissues. Statistical analysis showed that the expression of OLA1 was negatively correlated with the overall survival of hepatocellular carcinoma(P<0.01).OLA1 gene expression levels were significantly correlated to TNM stage, tumor differentiation, vascular invasion and poor prognosis in hepatocellular carcinoma(P<0.01). Correlation analysis showed that lncrna MALAT1 was negatively correlated with miR-144-3p and positively correlated with OLA1 gene in hepatocellular carcinoma(P<0.01). Conclusion OLA1 may play a promoting role in the occurrence and development of hepatocellular carcinoma through MALAT1-miR-144-3p axis. It may become a molecular marker for diagnosis and prognosis of hepatocellular carcinoma.