目的： 探讨P53 抑制肺腺癌A549细胞干细胞特性及其机制。方法： 收集2014年3月至2015年12月解放军第85医院胸外科手术切除的30例非小细胞肺癌（non-small cell lung carcinoma, NSCLC）患者癌组织及癌旁组织，采用Real-time PCR检测NSCLC组织和癌旁组织中miR-145的表达。构建人P53 基因的真核表达载体（pcDNA3.1-P53）和突变载体\[pcDNA3.1-P53 R273H(CGT-CAT)\]，设计靶向P53基因的siRNA，分别转染A549细胞；细胞分为对照转染组（Vector或NC-siRNA）和实验组（Flag-P53或P53-siRNA）；Western blotting检测P53蛋白过表达和干扰效率，Real-time PCR检测OCT4和miR-145的表达，荧光双报告基因和Western blotting技术检测证实A549细胞中干细胞多能性调节基因（OCT4）为miR-145的靶标分子。结果： NSCLC组织中miR-145的表达水平明显低于癌旁组织\[(2.31±0.13) vs (3.51±0.27)，P<0.01\]；P53明显促进A549细胞中miR-145的表达\[(1.84±0.14) vs (1.00±0.00)，P<0.01\]；miR-145 mimics显著抑制A549细胞中pGL3-OCT4-3′-UTR活性(P<001)和OCT4蛋白表达水平(P<0.05)，而转染miR-145抑制剂可进一步增加OCT4表达水平，且逆转P53对A549细胞的干细胞特性的抑制作用。结论：P53通过促进miR-145表达下调OCT4表达，进而明显抑制A549细胞的干细胞特性，该结果为肺腺癌的临床诊断和治疗提供了新途径。

Objective:To investigate the mechanism of P53 regulating stem cell characteristics of lung adenocarcinoma A549 cells. Methods: Carcinoma tissues and relevant para-carcinoma tissues from 30 non-small cell lung carcinoma (NSCLC) patients who underwent surgical resection at No.85 Military Hospital from March 2014 to December 2015 were collected for this study; Levels of miR-145 in collected tissues were determined by Real-time PCR. Human P53 gene eukaryotic expression vector (pcDNA3.1-P53), mutant vector \[pcDNA3.1-P53R273H(CGT-CAT)\] and siRNA that trageting P53 (P53-siRNA) were constructed and transfected into A549 cells. The cells were divided into transfection group (vector or NC-siRNA) and experiment group (Flag-P53 or P53-siRNA). Western blotting was used to examine P53 protein over-expression and interference efficiency; Real-time PCR was used to determine the expressions of miR-145 and OCT4. Dual-luciferase reporter and Western blotting were used to confirm that miR-145 directly targeted OCT4 in A549 cells. Results: Compared with para-carcinoma tissues, miR-145 was obviously decreased in NSCLC samples (\[231±013\] vs \[3.51±0.27\], P<0.01), and P53 significantly promoted miR-145 expression in A549 cells (\[184±0.14\] vs \[1.00±0.00\], P<0.01); miR-145 mimics significantly inhibited the activity of pGAL3-OCT4-3′-UTR (P<0.01) and protein expression of OCT4 (P<0.05) in A549 cells. Additionally, miR-145 inhibitor transfection further increased OCT4 expression and reversed the inhibitory effect of P53 on stem cell characteristics of A549 cells.Conclusion: P53 down-regulats OCT4 expression by promoting miR-145 expression, and further suppresses the stem cell characteristics of A549 cells, which might be a new and safe treatment approach for NSCLC.