过表达KLF4抑制非小细胞肺癌增殖及上皮间质转化的作用机制

Mechanisms of KLF4 over-expression in inhibiting proliferation and EMT of NSCLC

摘要:

目的探究KLF4 调控非小细胞肺癌（NSCLC）增殖及上皮间质转化（EMT）发生的作用机制，为NSCLC 的临床研究提供理论依据。方法收集临床病理资料进行统计学分析，免疫组织化学检测KLF4 在癌旁及癌组织中的表达，细胞水平检测KLF4 在癌细胞和正常细胞中的表达差异，过表达KLF4 检测对肺癌细胞的增殖、侵袭、迁移及EMT 相关标志物的影响。结果KLF4 在癌组织中的表达低于癌旁组织中的表达，并且与患者的临床分期及远处转移密切相关，细胞水平检测也得到了相同的结果，上调KLF4 的表达抑制了细胞的增殖、侵袭及迁移，同时抑制EMT 相关的间充质标志物的表达，促进上皮标志物的表达。结论过表达KLF4能够抑制NSCLC 增殖及EMT 的发生。

Abstract:

Objective To explore the effect of KLF4 on proliferation and epithelial mesenchymal transition (EMT) innon-small cell lung cancer (NSCLC). Methods KLF4 expression in 100 samples of surgical resected NSCLC and matched normal tumor-adjacent tissues were measured by immunohistochemical staining. KLF4 expression in WI-38 and NSCLC cell lines was detected by Western blot. The regulatory effect of KLF4 on proliferation, invasion,migration and EMT markers were confirmed by cell counting, Transwell and Western blot, respectively. Results KLF4 expression was impaired in the NSCLC tissues. Loss of KLF4 expression was correlated with poor clinicopathological features including tumor stage and distant metastasis, upregulated KLF4 attenuated proliferation,invasion and migration. Meanwhile, the expressions of N-cadherin and vimentin were markedly decreased, but Ecaherin and α-catenin expressions were increased after NSCLC cells were transfected with pMXs -hKLF4. Conclusions Our work provides a novel molecular insight into KLF4-directed tumor suppression through regulation of EMT.