miR-486-5p attenuates tumor growth and lymphangiogenesis by targeting neuropilin-2 in colorectal carcinoma

被引:58
作者
Liu, Chengxia [1 ]
Li, Ming [1 ]
Hu, Yingbin [1 ]
Shi, Ning [1 ]
Yu, Haisheng [1 ]
Liu, Haiyan [1 ]
Lian, Haifeng [1 ]
机构
[1] Binzhou Med Univ, Affiliated Hosp, Dept Gastroenterol, 661 Huanghe 2nd Rd, Binzhou 256603, Shandong, Peoples R China
关键词
miR-486-5p; colorectal carcinoma; neuropilin-2; tumor growth; lymphangiogenesis; BREAST-CANCER CELLS; DOWN-REGULATION; COLON-CANCER; METASTASIS; EXPRESSION; MICRORNA-486-5P; ANGIOGENESIS; PROGRESSION; RECEPTORS;
D O I
10.2147/OTT.S103460
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
Increasing evidence suggests that microRNAs are associated with many important biologic processes in carcinogenesis. Despite ample research revealing the dysregualtion of miR-486-5p in various cancers, little is known about the roles of miR-486-5p in colorectal carcinoma (CRC). In this study, we investigated the biological functions and molecular mechanisms of miR-486-5p in CRC growth and invasion, discussing the potential of using miR-486-5p as a biomarker for colorectal cancers. Our data revealed that miR-486-5p was significantly downregulated in CRC tissues compared with the paracancer tissue by quantitative real-time polymerase chain reaction and that miR-486-5p was downregulated to a greater extent in advanced stage cancer (stage III and IV) as compared to early stage cancer (stage I and II). Luciferase reporter assay verified that neuropilin-2 was a direct functional target of miR-486-5p in the CRC cells, and upregulation of miR-486-5p in CRC cells negatively correlated with the expression of neuropilin-2. Furthermore, overexpression of miR-486-5p inhibited the tumor growth and lymphangiogenesis in nude mice, which was reversed by overexpression of neuropilin-2. Taken together, our study suggested miR-486-5p might be a suppressor of CRC.
引用
收藏
页码:2865 / 2871
页数:7
相关论文
共 26 条
[1]   Neuropilins in neoplasms: Expression, regulation, and function [J].
Bielenberg, DR ;
Pettaway, CA ;
Takashima, S ;
Klagsbrun, M .
EXPERIMENTAL CELL RESEARCH, 2006, 312 (05) :584-593
[2]   Blocking neuropilin-2 function inhibits tumor cell metastasis [J].
Caunt, Maresa ;
Mak, Judy ;
Liang, Wei-Ching ;
Stawicki, Scott ;
Pan, Qi ;
Tong, Raymond K. ;
Kowalski, Joe ;
Ho, Calvin ;
Reslan, Hani Bou ;
Ross, Jed ;
Berry, Leanne ;
Kasman, Ian ;
Zlot, Constance ;
Cheng, Zhiyong ;
Le Couter, Jennifer ;
Filvaroff, Ellen H. ;
Plowman, Greg ;
Peale, Franklin ;
French, Dorothy ;
Carano, Richard ;
Koch, Alexander W. ;
Wu, Yan ;
Watts, Ryan J. ;
Tessier-Lavigne, Marc ;
Bagri, Anil .
CANCER CELL, 2008, 13 (04) :331-342
[3]   The evolution of gene regulation by transcription factors and microRNAs [J].
Chen, Kevin ;
Rajewsky, Nikolaus .
NATURE REVIEWS GENETICS, 2007, 8 (02) :93-103
[4]   Functional significance of vascular endothelial growth factor receptors on gastrointestinal cancer cells [J].
Dallas, Nikolaos A. ;
Fan, Fan ;
Gray, Michael J. ;
Van Buren, George, II ;
Lim, Sherry J. ;
Xia, Ling ;
Ellis, Lee M. .
CANCER AND METASTASIS REVIEWS, 2007, 26 (3-4) :433-441
[5]   Neuropilin-2-Mediated Tumor Growth and Angiogenesis in Pancreatic Adenocarcinoma [J].
Dallas, Nikolaos A. ;
Gray, Michael J. ;
Xia, Ling ;
Fan, Fan ;
van Buren, George ;
Gaur, Puja ;
Samuel, Shaija ;
Lim, Sherry J. ;
Arumugam, Thiruvengadam ;
Ramachandran, Vijaya ;
Wang, Huamin ;
Ellis, Lee M. .
CLINICAL CANCER RESEARCH, 2008, 14 (24) :8052-8060
[6]   Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012 [J].
Ferlay, Jacques ;
Soerjomataram, Isabelle ;
Dikshit, Rajesh ;
Eser, Sultan ;
Mathers, Colin ;
Rebelo, Marise ;
Parkin, Donald Maxwell ;
Forman, David ;
Bray, Freddie .
INTERNATIONAL JOURNAL OF CANCER, 2015, 136 (05) :E359-E386
[7]   MicroRNA-486-5p, which is downregulated in hepatocellular carcinoma, suppresses tumor growth by targeting PIK3R1 [J].
Huang, Xin-Ping ;
Hou, Jin ;
Shen, Xiao-Yun ;
Huang, Chao-Yuan ;
Zhang, Xue-Hui ;
Xie, Yu-An ;
Luo, Xiao-Ling .
FEBS JOURNAL, 2015, 282 (03) :579-594
[8]   Neuropilin-2 expression is inhibited by secreted Wnt antagonists and its down-regulation is associated with reduced tumor growth and metastasis in osteosarcoma [J].
Ji, Tao ;
Guo, Yi ;
Kim, Kapjun ;
McQueen, Peter ;
Ghaffar, Samia ;
Christ, Alexander ;
Lin, Carol ;
Eskander, Ramez ;
Zi, Xiaolin ;
Hoang, Bang H. .
Molecular Cancer, 2015, 14
[9]   Primary colon cancer: ESMO Clinical Practice Guidelines for diagnosis, adjuvant treatment and follow-up [J].
Labianca, R. ;
Nordlinger, B. ;
Beretta, G. D. ;
Brouquet, A. ;
Cervantes, A. .
ANNALS OF ONCOLOGY, 2010, 21 :v70-v77
[10]   The DNA methylation-regulated miR-193a-3p dictates the multi-chemoresistance of bladder cancer via repression of SRSF2/PLAU/HIC2 expression [J].
Lv, L. ;
Deng, H. ;
Li, Y. ;
Zhang, C. ;
Liu, X. ;
Liu, Q. ;
Zhang, D. ;
Wang, L. ;
Pu, Y. ;
Zhang, H. ;
He, Y. ;
Wang, Y. ;
Yu, Y. ;
Yu, T. ;
Zhu, J. .
CELL DEATH & DISEASE, 2014, 5 :e1402-e1402