miR-155/PTEN调控轴在肝癌中的表达及其机制

徐钢; 高轶; 闫茂生

doi:10.3971/j.issn.1000-8578.2018.17.0931

miR-155/PTEN调控轴在肝癌中的表达及其机制

Expression of miR-155/PTEN Axis in Hepatocellular Carcinoma and Its Mechanism

摘要

摘要:
目的检测microRNA-155（miR-155）在肝细胞癌中的表达并探讨其生物学作用及机制。
方法采用荧光定量PCR法检测miR-155在30对肝细胞癌和癌旁组织中的表达。在体外实验中，采用miR-155 mimic过表达miR-155，利用CCK-8和Transwell实验检测细胞增殖和迁移的变化。采用生物信息学和荧光素酶报告基因实验预测和验证miR-155的靶基因人第10号染色体缺失的磷酸酶及张力蛋白同源物基因（PTEN），并分析其生物学作用。应用cBioPortal数据库分析miR-155及PTEN对肝癌患者预后的影响。
结果 miR-155在肝癌组织中较癌旁组织表达升高（P < 0.0001），过表达miR-155能促进肝癌细胞的增殖和迁移。miR-155高表达患者的疾病无进展生存期（DFS）较低表达组显著降低（P=0.021）。miR-155直接负性调控PTEN的表达，并增强胞内磷脂酰肌醇激酶（PI3K）通路信号。PTEN表达缺失患者的疾病无进展生存期较PTEN表达正常组差（P=0.0133）。
结论 miR-155/PTEN调控轴对肝癌的进展发挥促进作用。

Abstract:
Objective To detect the expression and the function of microRNA-155(miR-155) in hepatocellular carcinoma(HCC) tissuse, and to elucidate related mechanism.
Methods miR-155 expression was examined in 30 pairs of HCC and adjacent normal tissues by quantitative reverse transcription PCR(qRT-PCR). HCC cells were treated with miR-155 mimic to upregulate miR-155 expression in vitro. CCK-8 and Transwell assays were used to analyze the changes in cell proliferation and migration. PTEN was predicted to be the direct target of miR-155 by bioinformatics analysis and luciferase reporter assay. The prognostic value of miR-155 and PTEN in patients with HCC were assessed through cBioPortal database.
Results miR-155 was significantly upregulated in HCC tissues compared with that in adjacent normal tissues (P < 0.0001). Overexpression of miR-155 was associated with worse disease free survival (P=0.021). Elevated expression of miR-155 promoted the proliferation and migration of hepatocellular carcinoma cells. Furthermore, miR-155 directly repressed PTEN expression, which enhanced PI3K signaling pathway. Deletion of PTEN depicted worse disease free survival in patients with HCC (P=0.0133).
Conclusion The axis of miR-155/PTEN accelerates HCC progression.

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