miR-539通过靶向调控DCLK1抑制非小细胞肺癌的侵袭能力

miR-539 inhibiting the invasion ability of non-small-cell lung cancer cells by targeting DCLK1

目的探讨非小细胞肺癌组织中miR-539的表达水平及其抑制肺癌细胞侵袭的作用机制。方法通过基因表达数据库dbDEMC分析miR-539在非小细胞肺癌组织及正常肺组织中的表达量差异。根据235例miR-539高表达的非小细胞肺癌患者和102例miR-539低表达的非小细胞肺癌患者随访资料,分析miR-539与非小细胞肺癌患者预后的相关性。利用生物信息预测结合双荧光素酶报告基因实验研究miR-539的潜在靶基因。在肺癌A549细胞中分别过表达miR-539、转染miR-539抑制剂,利用Transwell法检测肺癌A549细胞的侵袭能力。结果dbDEMC数据库资料显示miR-539在非小细胞肺癌组织中的表达量显著低于其在正常肺组织中的表达量(P=3.10×10-4)。生存分析发现miR-539的表达量与肺癌患者预后正相关(P=0.033)。通过在线生物信息学预测结合双荧光素报告实验发现miR-539在转录水平减少DCLK1的表达。Transwell侵袭实验发现,过表达miR-539可以抑制肺癌A549细胞的侵袭能力,而沉默miR-539可以增加A549细胞的侵袭能力。结论miR-539是肺癌发生中的抑癌基因,可能是通过靶向沉默DCLK1的表达,而抑制肺癌细胞A549的侵袭能力。

Objective To investigate the expression level of miR-539 in non-small cell lung cancer and the possible mechanism of miR-539 inhibiting the invasion ability of lung cancer cells.Methods The expression of miR-539 in non-small cell lung cancer tissue and normal lung tissue was analyzed by the gene expression database dbDEMC.According to the follow-up data of 235 NSCLC patients with high expression of miR-539 and 102 NSCLC patients with with low expression of miR-539,the correlation between the expression of miR-539 and prognosis of NSCLC patients was analyzed.Biological information in tool combination with a dual luciferase reporter gene experiment was used to predict the potential target genes of miR-539.Transwell cell invasion experiment was used to detect the influence of miR-539 on invasion ability of lung cancer A549 cells.Results The dbDEMC database data showed that the expression of miR-539 in non-small cell lung cancer tissues was significantly lower than that in normal lung tissues(P=3.10×10-4).Survival analysis showed that the expression of miR-539 was positively correlated with the prognosis of patients with lung cancer(P=0.033).Online bioinformatics prediction tool combined with the dual luciferin reporting test found that miR-539 reduced DCLK1 expression at the transcription level.Transwell cell invasion experiments found that over-expression of miR-539 could inhibit the invasion ability of lung cancer A549 cells,while silencing miR-539 could increase the invasion ability of A549 cells.Conclusion miR-539 is a tumor suppressor gene in the development of lung cancer,which may inhibit the invasion ability of lung cancer cell A549 by targeting the silence of DCLK1 expression.