Zhou Shixia, Zhang Zhongmian, Zheng Pengyuan, Zhao Wenchao, Han Na
1 Department of Oncology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
2 Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Tumour Biol. 2017 Jun;39(6):1010428317705513. doi: 10.1177/1010428317705513.
Abnormal expression of microRNAs has been reported to regulate gene expression and cancer cell growth, invasion, and migration. Recently, upregulation of hsa-miR-1285 was demonstrated in bronchoalveolar lavage fluid samples from patients with lung cancer and downregulation in plasma level of stage-I lung cancer patients. However, the function and the underlying mechanism of miR-1285 in non-small-cell lung carcinoma have not been elucidated. In this study, we found that miR-1285-5p, the mature form of miR-1285, was significantly upregulated in human non-small-cell lung carcinoma cell lines A549 and SK-MES-1. Additionally, cells transfected with the miR-1285-5p inhibitor LV-anti-miR-1285-5p demonstrated significantly inhibited proliferation and invasion and depressed migration. Further analysis demonstrated that the miR-1285-5p precursor LV-miR-1285-5p attenuated the expression of Smad4 and cadherin-1 (CDH1) but that LV-anti-miR-1285-5p showed opposite results. A luciferase reporter assay confirmed that miR-1285-5p targeted Smad4 and CDH1. Mechanism analyses revealed that silence of Smad4 and CDH1 significantly attenuated the inhibitory effects of LV-anti-miR-1285-5p on non-small-cell lung carcinoma growth and invasion. Taken together, our data suggest that miR-1285-5p functions as a tumor promoter in the development of non-small-cell lung carcinoma by targeting Smad4 and CDH1, indicating a novel therapeutic strategy for non-small-cell lung carcinoma patients.
据报道，微小RNA的异常表达可调节基因表达以及癌细胞的生长、侵袭和迁移。最近，在肺癌患者的支气管肺泡灌洗液样本中证实了hsa-miR-1285的上调，而在I期肺癌患者的血浆水平中则下调。然而，miR-1285在非小细胞肺癌中的功能及潜在机制尚未阐明。在本研究中，我们发现miR-1285的成熟形式miR-1285-5p在人非小细胞肺癌细胞系A549和SK-MES-1中显著上调。此外，用miR-1285-5p抑制剂LV-anti-miR-1285-5p转染的细胞表现出增殖和侵袭明显受到抑制，迁移能力下降。进一步分析表明，miR-1285-5p前体LV-miR-1285-5p可减弱Smad4和钙黏蛋白-1（CDH1）的表达，但LV-anti-miR-1285-5p则呈现相反结果。荧光素酶报告基因检测证实miR-1285-5p靶向Smad4和CDH1。机制分析显示，沉默Smad4和CDH1可显著减弱LV-anti-miR-1285-5p对非小细胞肺癌生长和侵袭的抑制作用。综上所述，我们的数据表明，miR-1285-5p通过靶向Smad4和CDH1在非小细胞肺癌的发生发展中发挥肿瘤促进作用，这为非小细胞肺癌患者提供了一种新的治疗策略。
