MicroRNA-29a plays a suppressive role in non-small cell lung cancer cells via targeting LASP1

被引:22
作者
Hu, Zhaolan [1 ]
Cui, Yanhui [1 ]
Zhou, Yanhui [2 ]
Zhou, Kaiying [3 ]
Qiao, Xiaoqing [1 ]
Li, Changqi [1 ]
Wang, Shuang [4 ,5 ]
机构
[1] Cent South Univ, Dept Anat & Neurobiol, Sch Basic Med Sci, Changsha, Hunan, Peoples R China
[2] Cent South Univ, XiangYa Nursing Sch, Changsha, Hunan, Peoples R China
[3] Peoples Hosp Lianyuan, Dept Orthopaed, Lianyuan, Peoples R China
[4] Cent South Univ, Med Res Ctr, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China
[5] Cent South Univ, Clin Lab, Xiangya Hosp, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China
关键词
non-small cell lung cancer; microRNA-29a; LIM and SH3 protein 1; proliferation; migration; invasion; PROLIFERATION; EXPRESSION; MIGRATION; PROMOTES; INVASION; MIR-29; GROWTH; LIM;
D O I
10.2147/OTT.S116509
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
MicroRNA (miR)-29a has been implicated in non-small cell lung cancer (NSCLC), but the mechanism remains largely unclear. LASP1, a cAMP-and cGMP-dependent signaling protein, was recently found to promote proliferation and aggressiveness in NSCLC. However, the regulatory mechanism of LASP1 expression in NSCLC, as well as the relationship between LASP1 and miR-29a, has never been previously studied. In this study, we found that miR-29a was remarkably downregulated and low expression of miR-29a was associated with the malignant progression of NSCLC. Moreover, the expression of LASP1 was markedly increased in NSCLC tissues and cell lines. Bioinformatics analysis and luciferase reporter assay data further identified LASP1 as a target gene of miR-29a, and the expression of LASP1 was negatively mediated by miR-29a at the post-transcriptional level in NSCLC cells. Overexpression of miR-29a reduced the proliferation, migration, and invasion of NSCLC cells, just as the effects of LASP1 knockdown. Moreover, overexpression of LASP1 attenuated the suppressive effect of miR-29a on the malignant phenotypes of NSCLC cells. In addition, upregulation of miR-29a decreased the growth of A549 cells in nude mice and protected the animals from tumor-induced death. Therefore, we demonstrate that miR-29a plays a suppressive role in NSCLC via targeting LASP1, suggesting that the miR-29a/LASP1 axis may become a promising therapeutic target for NSCLC.
引用
收藏
页码:6999 / 7009
页数:11
相关论文
共 27 条
[1]   The functions of animal microRNAs [J].
Ambros, V .
NATURE, 2004, 431 (7006) :350-355
[2]   Low miR-145 and high miR-367 are associated with unfavourable prognosis in resected nonsmall cell lung cancer [J].
Campayo, Marc ;
Navarro, Alfons ;
Vinolas, Nuria ;
Diaz, Tania ;
Tejero, Rut ;
Gimferrer, Josep M. ;
Molins, Laureano ;
Cabanas, Maria L. ;
Ramirez, Jose ;
Monzo, Mariano ;
Marrades, Ramon .
EUROPEAN RESPIRATORY JOURNAL, 2013, 41 (05) :1172-1178
[3]   Let-7g and miR-21 expression in non-small cell lung cancer: Correlation with clinicopathological and molecular features [J].
Capodanno, Alessandra ;
Boldrini, Laura ;
Proietti, Agnese ;
Ali, Greta ;
Pelliccioni, Serena ;
Niccoli, Cristina ;
D'Incecco, Armida ;
Cappuzzo, Federico ;
Chella, Antonio ;
Lucchi, Marco ;
Mussi, Alfredo ;
Fontanini, Gabriella .
INTERNATIONAL JOURNAL OF ONCOLOGY, 2013, 43 (03) :765-774
[4]   Loss of miR-200c Expression Induces an Aggressive, Invasive, and Chemoresistant Phenotype in Non-Small Cell Lung Cancer [J].
Ceppi, Paolo ;
Mudduluru, Giridhar ;
Kumarswamy, Regalla ;
Rapa, Ida ;
Scagliotti, Giorgio V. ;
Papotti, Mauro ;
Allgayer, Heike .
MOLECULAR CANCER RESEARCH, 2010, 8 (09) :1207-1216
[5]   miRNA-145 inhibits non-small cell lung cancer cell proliferation by targeting c-Myc [J].
Chen, Zhe ;
Zeng, Huazong ;
Guo, Yong ;
Liu, Pei ;
Pan, Hui ;
Deng, Anmei ;
Hu, Jian .
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2010, 29
[6]   MiR-29a Inhibits Cell Proliferation and Induces Cell Cycle Arrest through the Downregulation of p42.3 in Human Gastric Cancer [J].
Cui, Yun ;
Su, Wen-Yu ;
Xing, Jing ;
Wang, Ying-Chao ;
Wang, Ping ;
Chen, Xiao-Yu ;
Shen, Zhi-Yong ;
Cao, Hui ;
Lu, You-Yong ;
Fang, Jing-Yuan .
PLOS ONE, 2011, 6 (10)
[7]   The tumor-suppressive function of miR-1 by targeting LASP1 and TAGLN2 in esophageal squamous cell carcinoma [J].
Du, Yan-Yan ;
Zhao, Lian-Mei ;
Chen, Liang ;
Sang, Mei-Xiang ;
Li, Jie ;
Ma, Ming ;
Liu, Jun-Feng .
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 2016, 31 (02) :384-393
[8]   Cancer statistics, 2000 [J].
Greenlee, RT ;
Murray, T ;
Bolden, S ;
Wingo, PA .
CA-A CANCER JOURNAL FOR CLINICIANS, 2000, 50 (01) :7-33
[9]   FOXO3A Regulation by miRNA-29a Controls Chondrogenic Differentiation of Mesenchymal Stem Cells and Cartilage Formation [J].
Guerit, David ;
Brondello, Jean-Marc ;
Chuchana, Paul ;
Philipot, Didier ;
Toupet, Karine ;
Bony, Claire ;
Jorgensen, Christian ;
Noel, Daniele .
STEM CELLS AND DEVELOPMENT, 2014, 23 (11) :1195-1205
[10]   Angiogenesis inhibition as a therapeutic strategy in non-small cell lung cancer (NSCLC) [J].
Hall, Richard D. ;
Le, Tri M. ;
Haggstrom, Daniel E. ;
Gentzler, Ryan D. .
TRANSLATIONAL LUNG CANCER RESEARCH, 2015, 4 (05) :515-523