Identification of microRNA-615-3p as a novel tumor suppressor in non-small cell lung cancer

被引:31
作者
Pu, Heng-Ying [1 ,2 ]
Xu, Rui [3 ]
Zhang, Mei-Yin [1 ,2 ]
Yuan, Lin-Jing [1 ,2 ]
Hu, Jing-Ye [4 ]
Huang, Guo-Liang [5 ]
Wang, Hui-Yun [1 ,2 ]
机构
[1] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Room 704,West Bldg,651 Dongfeng East Rd, Guangzhou 510060, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Ctr Canc, Collaborat Innovat Ctr Canc Med, Guangzhou, Guangdong, Peoples R China
[3] Guangzhou Med Univ, Dept Internal Med, Ctr Canc, Guangzhou 510060, Guangdong, Peoples R China
[4] Guiyang Coll Tradit Chinese Med, Dept Basic Med, Guiyang 550000, Guizhou, Peoples R China
[5] Guangdong Med Coll, Sinoamer Canc Res Inst, Dongguan 523808, Guangdong, Peoples R China
关键词
miR-615-3p; non-small cell lung cancer; RT-qPCR; microarray; biological role; DIAGNOSIS; SIGNATURE;
D O I
10.3892/ol.2017.5684
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Lung cancer is the most frequent cause of mortality in cancer patients; non-small-cell lung cancer (NSCLC) accounts for similar to 80% of lung cancer cases. MicroRNAs (miRNAs) have been revealed to perform an important role in cancer development and progression. Based on a custom miRNA microarray analysis of patients with NSCLC, miRNA-615-3p (miR-615-3p) downregulation was identified in NSCLC tissues compared with normal lung tissues, which suggested that miR-615-3p acted as a tumor suppressor in lung cancer. The overexpression of miR-615-3p was then validated using 40 pairs of NSCLC and adjacent normal tissue samples using a TaqMan reverse transcription-quantitative polymerase chain reaction assay. In order to investigate the tumor suppressor function of miR-615-3p, the ectopic expression of miR-615-3p in the NSCLC A549, H1299 and H1650 cell lines was established. The results revealed that overexpressed miR-615-3p markedly inhibited cell proliferation and colony formation in the 3 NSCLC cell lines compared with the cells overexpressing the negative control sequence (NC). Additional investigation revealed that miR-615-3p overexpression significantly induced apoptosis and cell cycle arrest at the G1 phase in the A549, H1299 and H1650 cell lines compared with the cells overexpressing NC. Finally, ectopic expression of miR-615-3p was found to repress the cell migration and invasion of the 3 lung cancer cell lines. The results of the present study demonstrate, for the first time, that miR-615-3p functions as a tumor suppressor in NSCLC, and may be a novel potential molecular therapeutic target for patients with NSCLC.
引用
收藏
页码:2403 / 2410
页数:8
相关论文
共 15 条
[1]   Preoperative chemotherapy for non-small-cell lung cancer: a systematic review and meta-analysis of individual participant data [J].
Burdett, Sarah ;
Rydzewska, Larysa H. M. ;
Tierney, Jayne F. ;
Auperin, Anne ;
Le Pechoux, Cecile ;
Le Chevalier, Thierry ;
Pignon, Jean-Pierre .
LANCET, 2014, 383 (9928) :1561-1571
[2]   MicroRNA signatures in human cancers [J].
Calin, George A. ;
Croce, Carlo M. .
NATURE REVIEWS CANCER, 2006, 6 (11) :857-866
[3]   The American Joint Committee on Cancer: the 7th Edition of the AJCC Cancer Staging Manual and the Future of TNM [J].
Edge, Stephen B. ;
Compton, Carolyn C. .
ANNALS OF SURGICAL ONCOLOGY, 2010, 17 (06) :1471-1474
[4]   Oncomirs - microRNAs with a role in cancer [J].
Esquela-Kerscher, A ;
Slack, FJ .
NATURE REVIEWS CANCER, 2006, 6 (04) :259-269
[5]   Deregulated expression of miR-21, miR-143 and miR-181a in non small cell lung cancer is related to clinicopathologic characteristics or patient prognosis [J].
Gao, Wen ;
Yu, Yue ;
Cao, Hailong ;
Shen, Hua ;
Li, Xiaodong ;
Pan, Shiyang ;
Shu, Yongqian .
BIOMEDICINE & PHARMACOTHERAPY, 2010, 64 (06) :399-408
[6]   MicroRNA Signature Obtained From the Comparison of Aggressive With Indolent Non-Hodgkin Lymphomas: Potential Prognostic Value in Mantle-Cell Lymphoma [J].
Goswami, Rashmi S. ;
Atenafu, Eshetu G. ;
Xuan, Yali ;
Waldron, Levi ;
Reis, Patricia P. ;
Sun, Thomas ;
Datti, Alessandro ;
Xu, Wei ;
Kuruvilla, John ;
Good, David J. ;
Lai, Raymond ;
Church, Alanna J. ;
Lam, Wilson S. ;
Baetz, Tara ;
LeBrun, David P. ;
Sehn, Laurie H. ;
Farinha, Pedro ;
Jurisica, Igor ;
Bailey, Denis J. ;
Gascoyne, Randy D. ;
Crump, Michael ;
Kamel-Reid, Suzanne .
JOURNAL OF CLINICAL ONCOLOGY, 2013, 31 (23) :2903-+
[7]   CDKN2A, NF2, and JUN Are Dysregulated Among Other Genes by miRNAs in Malignant Mesothelioma-A miRNA Microarray Analysis [J].
Guled, Mohamed ;
Lahti, Leo ;
Lindholm, Pamela M. ;
Salmenkivi, Kaisa ;
Bagwan, Izhar ;
Nicholson, Andrew G. ;
Knuutila, Sakari .
GENES CHROMOSOMES & CANCER, 2009, 48 (07) :615-623
[8]  
JEMAL A, 2011, CA-CANCER J CLIN, V61, P134, DOI [DOI 10.3322/CAAC.20107, DOI 10.3322/caac.20115]
[9]   Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method [J].
Livak, KJ ;
Schmittgen, TD .
METHODS, 2001, 25 (04) :402-408
[10]   Clinical evaluation of microRNA expression profiling in non small cell lung cancer [J].
Markou, A. ;
Sourvinou, I. ;
Vorkas, P. A. ;
Yousef, G. M. ;
Lianidou, E. .
LUNG CANCER, 2013, 81 (03) :388-396