Hou Yan, Zhen Junwen, Xu Xiaodong, Zhen Kun, Zhu Bin, Pan Rui, Zhao Chidong
Department of Pediatrics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China ; Department of Pediatrics, Central Hospital, Xiangyang, Hubei 441021, P.R. China.
Department of Pediatrics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
Oncol Lett. 2015 Oct;10(4):1985-1992. doi: 10.3892/ol.2015.3587. Epub 2015 Aug 11.
MicroRNA-215 (miR-215) has previously been demonstrated to be dysregulated in a number of human malignancies and to be correlated with tumor progression. However, the expression and function of miR-215 in non-small cell lung cancer (NSCLC) has remained to be elucidated. Therefore, the present study aimed to investigate the effects of miR-215 in NSCLC tumorigenesis and development. Reverse transcription-quantitative polymerase chain reaction was used to evaluate miR-215 expression in NSCLC cell lines and primary tumor tissues. The association between miR-215 expression and certain clinicopathological factors was also determined, and the effects of miR-215 on the biological behavior of NSCLC cells were investigated. In addition, the potential regulatory function of miR-215 on zinc finger E-box-binding homeobox 2 (ZEB2) expression was examined. miR-215 expression was significantly downregulated in NSCLC cell lines and clinical specimens. Reduced miR-215 expression was significantly associated with lymph node metastasis and advanced TNM stage. Overexpression of miR-215 inhibited NSCLC cell proliferation, invasion and migration, and promoted cell apoptosis , and suppressed tumorigenicity . Furthermore, luciferase reporter assay analysis identified ZEB2 as a direct target of miR-215. These findings indicated that miR-215 may act as a tumor suppressor in NSCLC and may serve as a novel therapeutic agent for miR-based therapy.
此前已有研究表明,微小RNA-215(miR-215)在多种人类恶性肿瘤中表达失调,并与肿瘤进展相关。然而,miR-215在非小细胞肺癌(NSCLC)中的表达及功能仍有待阐明。因此,本研究旨在探讨miR-215在NSCLC发生发展中的作用。采用逆转录-定量聚合酶链反应评估NSCLC细胞系和原发性肿瘤组织中miR-215的表达。还确定了miR-215表达与某些临床病理因素之间的关联,并研究了miR-215对NSCLC细胞生物学行为的影响。此外,检测了miR-215对锌指E盒结合同源框2(ZEB2)表达的潜在调控作用。miR-215在NSCLC细胞系和临床标本中的表达显著下调。miR-215表达降低与淋巴结转移和TNM分期进展显著相关。miR-215过表达抑制NSCLC细胞增殖、侵袭和迁移,促进细胞凋亡,并抑制肿瘤发生。此外,荧光素酶报告基因分析确定ZEB2是miR-215的直接靶点。这些发现表明,miR-215可能在NSCLC中发挥肿瘤抑制作用,并可能成为基于miR的治疗的新型治疗药物。