This study aims to examine whether miR-448 reverses the cisplatin (DDP) resistance in lung cancer by modulating SATB1. QRT-PCR and immunohistochemistry were used to examine the miR-448 and SATB1 expressions in DDP-sensitive and -resistant lung cancer patients. A microarray was used to investigate the cytoplasmic/nucleic ratio (C/N ratios) of genes in A549 cells targeted by miR-448, followed by Dual-luciferase reporter gene assay. A549/DDP cells were transfected with miR-448 mimics/inhibitors with or without SATB1 siRNA followed by MTT assay, Edu staining, flow cytometry, qRT-PCR and western blotting. MiR-448 was lower but SATB1 was increased in DDP-resistant patients and A549/DDP cells. And the patients showed low miR-448 expression or SATB1 positive expression had poor prognosis. SATB1, as a target gene with higher C/N ratios (>1), was found negatively regulated by miR-448. Besides, miR-448 inhibitors increased resistance index of A549/DDP cells, promoted cell proliferation, increased cell distribution in S phrase, declined cell apoptosis and activated Wnt/β-catenin pathway. However, SATB1 siRNA could reverse the above effect caused by miR-448 inhibitors. MiR-448 targeting SATB1 to counteract the DDP resistance of lung cancer cells via Wnt/β-catenin pathway.

中文翻译：

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MicroRNA-448靶向SATB1，通过介导Wnt /β-catenin信号通路逆转肺癌的顺铂耐药性。

这项研究旨在检查miR-448是否通过调节SATB1逆转肺癌对顺铂（DDP）的耐药性。使用QRT-PCR和免疫组织化学检查在DDP敏感和耐药的肺癌患者中miR-448和SATB1的表达。使用微阵列研究了miR-448靶向的A549细胞中基因的细胞质/核酸比率（C / N比），然后进行了双重荧光素酶报告基因检测。A549 / DDP细胞用miR-448模拟物/抑制剂转染，含或不含SATB1 siRNA，然后进行MTT分析，Edu染色，流式细胞仪，qRT-PCR和Western blotting。MiR-448较低，但SATB1在耐DDP的患者和A549 / DDP细胞中，其升高。患者miR-448表达低或SATB1阳性表达预后不良。发现SATB1作为具有更高C / N比（> 1）的靶基因，被miR-448负调控。此外，miR-448抑制剂可提高A549 / DDP细胞的抵抗指数，促进细胞增殖，增加S短语中的细胞分布，降低细胞凋亡并激活Wnt /β-catenin途径。但是，SATB1 siRNA可以逆转由miR-448抑制剂引起的上述作用。靶向SATB1的MiR-448可通过Wnt /β-catenin途径抵消肺癌细胞的DDP抗性。