摘要目的 探讨微小RNA(miRNA,miR)-338-3p与肝癌发展中的作用机制.方法 收集经手术切除并病理证实的39例原发性肝癌组织标本及对应的21例癌旁组织标本,细胞培养肝癌细胞,应用实时定量反转录聚合酶链反应(RT-qPCR)检测组织及细胞中的miR-338-3p的表达,细胞计数试剂盒(CCK-8)和集落形成试验测定miR-338-3p对肝癌细胞生长的影响.采用生物信息学分析和荧光素酶报告基因检测检测miR-338-3p的靶点.结果 肝癌细胞和组织中miR-338-3p的表达均降低(1.37±0.05、0.95±0.03、1.15±0.09比3.38±0.11,t=5.235,P=0.019;0.89±0.08比2.03±0.05,t=3.535,P=0.008),miR-338-3p在肝癌细胞中的表达增强抑制了克隆的形成和细胞增殖.此外,miR-338-3p靶向调节鞘氨醇激酶2(SpHK2),SpHK2沉默对肝癌细胞中miR-338-3p的过表达具有相同的影响.SpHK2在3'非翻译区的过表达显著增强了miR-338-3p在肝癌细胞中的生长抑制作用.结论 miR-338-3p可以通过靶向调教SpHK2来影响肝癌的发展.

abstractsObjective Despite the fact that microRNA (miRNA,miR)-338-3p can play an important role in many kinds of tumors,whether it has an influence on liver cancer (LC) is undetermined.Methods In this study,the expression of miR 338-3p in human LC tissues and cells was determined by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) assay.The effect of miR-338-3p on LC cell growth was determined by cell counting kit-8 (CCK-8) and colony formation assay.Bioinformatic analysis,luciferase reporter assays and western blotting were used to determine the target of miR-338-3p.Results The expression of miR-338-3p was decreased in LC cells as well as tissues(1.37±0.05,0.95 ±0.03,1.15 ±0.09 vs.3.38±0.11,t=5.235,P=0.019;0.89 ±0.08 vs.2.03 ±0.05,t =3.535,P =0.008).Clone formation and cell proliferation are suppressed by enhanced expression of miR-338-3p in LC cells.Moreover,we found that miR-338-3p targeted sphingosine kinase 2 (SphK2).The silencing of SphK2 showed the identical influence to overexpression of miR-338-3p in LC cells.Overexpression of SphK2 without 3' untranslated region remarkably enhanced the growth suppression triggered by miR-338-3p in LC cells.Conclusion miR-338-3p could influence the development of LC through targeting SphK2,suggesting miR-338-3p could serve as an innovative therapeutic strategy in terms of LC.