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miR-215在人类非小细胞肺癌中作为一种肿瘤抑制因子发挥作用,并直接靶向ZEB2。

miR-215 functions as a tumor suppressor and directly targets ZEB2 in human non-small cell lung cancer.

作者信息

Hou Yan, Zhen Junwen, Xu Xiaodong, Zhen Kun, Zhu Bin, Pan Rui, Zhao Chidong

机构信息

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.

出版信息

Oncol Lett. 2015 Oct;10(4):1985-1992. doi: 10.3892/ol.2015.3587. Epub 2015 Aug 11.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8298/4579799/462a367aea6b/ol-10-04-1985-g00.jpg

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