Metastasis-associated miR-23a from nasopharyngeal carcinoma-derived exosomes mediates angiogenesis by repressing a novel target gene TSGA10

被引:219
作者
Bao, Lili [1 ]
You, Bo [1 ]
Shi, Si [1 ]
Shan, Ying [1 ]
Zhang, Qicheng [1 ]
Yue, Huijun [1 ]
Zhang, Jie [1 ]
Zhang, Wei [1 ]
Shi, Yunwei [2 ]
Liu, Yifei [3 ]
Wang, Xin [2 ]
Liu, Dong [2 ]
You, Yiwen [1 ]
机构
[1] Nantong Univ, Dept Otorhinolaryngol Head & Neck Surg, Affiliated Hosp, Xisi Rd 20, Nantong 226001, Peoples R China
[2] Nantong Univ, Coinnovat Ctr Neuroregenerat, Jiangsu Key Lab Neuroregenerat, Qixiu Rd 19, Nantong 226001, Peoples R China
[3] Nantong Univ, Dept Pathol, Affiliated Hosp, Xisi Rd 20, Nantong 226001, Peoples R China
基金
中国国家自然科学基金;
关键词
TUMOR ANGIOGENESIS; EXPRESSION; CANCER; MICRORNAS; CHEMOTHERAPY; OVEREXPRESSION; RADIOTHERAPY; METAANALYSIS; VESICLES; GROWTH;
D O I
10.1038/s41388-018-0183-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Benefiting from more precise imaging and radiotherapy, patients with locoregionally nasopharyngeal carcinoma (NPC) have a significantly higher survival rate. Nonetheless, distant metastasis is still the predominant mode of failure. Advances in cancer research have highlighted that pathological angiogenesis is necessary for tumor metastasis by offering oxygen, nutrients, or cell metastatic conduits. MicroRNAs (miRNAs), a class of small noncoding RNAs, are increasingly implicated in modulation of angiogenesis in physiological and pathological conditions. Currently, we detected that miR-23a was highly enriched in NPC tissues at the metastatic or premetastatic stage, and its levels in NPC were associated with microvessel density. Subsequently, we proved that alteration of miR-23a expression modulated the growth, migration, and tube formation of HUVECs in vitro and affected the blood vessel outgrowth in the zebrafish model. Considering the possibility that extracellular miR-23a was horizontally transferred from CNE2 cells to HUVECs, we analyzed miR-23a encapsulated in exosomes, showing that overexpression of exosomal miR-23a in NPC promoted angiogenesis both in vitro and in vivo. Moreover, we provided evidences that miR-23a regulated angiogenesis by directly targeting testis-specific gene antigen (TSGA10). Taken together, our findings revealed that metastasis-associated miR-23a from NPC-derived exosomes plays an important role in mediating angiogenesis by targeting TSGA10.
引用
收藏
页码:2873 / 2889
页数:17
相关论文
共 52 条
[1]
Intercellular transfer of the oncogenic receptor EGFrvIII by microvesicles derived from tumour cells [J].
Al-Nedawi, Khalid ;
Meehan, Brian ;
Micallef, Johann ;
Lhotak, Vladimir ;
May, Linda ;
Guha, Abhijit ;
Rak, Janusz .
NATURE CELL BIOLOGY, 2008, 10 (05) :619-U24
[2]
Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma [J].
Arroyo, Jason D. ;
Chevillet, John R. ;
Kroh, Evan M. ;
Ruf, Ingrid K. ;
Pritchard, Colin C. ;
Gibson, Donald F. ;
Mitchell, Patrick S. ;
Bennett, Christopher F. ;
Pogosova-Agadjanyan, Era L. ;
Stirewalt, Derek L. ;
Tait, Jonathan F. ;
Tewari, Muneesh .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (12) :5003-5008
[3]
Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences [J].
Balaj, Leonora ;
Lessard, Ryan ;
Dai, Lixin ;
Cho, Yoon-Jae ;
Pomeroy, Scott L. ;
Breakefield, Xandra O. ;
Skog, Johan .
NATURE COMMUNICATIONS, 2011, 2
[4]
Overexpression of IGFBP3 is associated with poor prognosis and tumor metastasis in nasopharyngeal carcinoma [J].
Bao, Lili ;
Liu, Hao ;
You, Bo ;
Gu, Miao ;
Shi, Si ;
Shan, Ying ;
Li, Li ;
Chen, Jing ;
You, Yiwen .
TUMOR BIOLOGY, 2016, 37 (11) :15043-15052
[5]
Chemotherapy in locally advanced nasopharyngeal carcinoma: An individual patient data meta-analysis of eight randomized trials and 1753 patients [J].
Baujat, B ;
Audry, W ;
Bourhis, J ;
Chan, ATC ;
Onat, H ;
Chua, DTT ;
Kwong, DLW ;
al-Sarraf, M ;
Chi, KH ;
Hareyama, M ;
Leung, SF ;
Thephamongkhol, K ;
Pignon, JP .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2006, 64 (01) :47-56
[6]
Angiogenesis in cancer and other diseases [J].
Carmeliet, P ;
Jain, RK .
NATURE, 2000, 407 (6801) :249-257
[7]
Origins and Mechanisms of miRNAs and siRNAs [J].
Carthew, Richard W. ;
Sontheimer, Erik J. .
CELL, 2009, 136 (04) :642-655
[8]
Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells [J].
Chalmin, Fanny ;
Ladoire, Sylvain ;
Mignot, Gregoire ;
Vincent, Julie ;
Bruchard, Melanie ;
Remy-Martin, Jean-Paul ;
Boireau, Wilfrid ;
Rouleau, Alain ;
Simon, Benoit ;
Lanneau, David ;
De Thonel, Aurelie ;
Multhoff, Gabriele ;
Hamman, Arlette ;
Martin, Francois ;
Chauffert, Bruno ;
Solary, Eric ;
Zitvogel, Laurence ;
Garrido, Carmen ;
Ryffel, Bernhard ;
Borg, Christophe ;
Apetoh, Lionel ;
Rebe, Cedric ;
Ghiringhelli, Francois .
JOURNAL OF CLINICAL INVESTIGATION, 2010, 120 (02) :457-471
[9]
Nasopharyngeal carcinoma [J].
Chan, A. T. C. .
ANNALS OF ONCOLOGY, 2010, 21 :308-312
[10]
αvβ3 Integrin and tumour blood vessels - learning from the past to shape the future [J].
Demircioglu, Fevzi ;
Hodivala-Dilke, Kairbaan .
CURRENT OPINION IN CELL BIOLOGY, 2016, 42 :121-127