Exosomes of glioma cells deliver miR-148a to promote proliferation and metastasis of glioblastoma via targeting CADM1

被引:87
作者
Cai, Qian [1 ]
Zhu, Anding [2 ]
Gong, Li [3 ]
机构
[1] Cent S Univ, Xiangya Hosp 3, Dept Pediat, Changsha 410013, Hunan, Peoples R China
[2] Cent S Univ, Xiangya Hosp 3, Dept Neurol, Changsha 410013, Hunan, Peoples R China
[3] Cent S Univ, Xiangya Hosp 3, Dept Anesthesiol, Changsha 410013, Hunan, Peoples R China
关键词
Glioma cells; miR-148a; Proliferation; Metastasis; CADM1; TUMOR-SUPPRESSOR; STAT3; ACTIVATION; INHIBITION; CANCER; PROGRESSION; EXPRESSION; MICRORNAS; CARCINOMA; GROWTH;
D O I
10.1016/j.bulcan.2018.05.003
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Exosomes are now considered to be involved in mediating cell-to-cell communication to promote or inhibit tumor progression. However, the role and molecular mechanism of exosomes in promoting glioblastoma (GBM) metastasis remains elusive. Here, we found that circulating exosomal miR-148a levels were significantly higher in serum from GBM patients compared with serum from healthy volunteers. In T98G cells, inhibition of miR-148a suppressed cell proliferation and metastasis. In addition, we identified Cell adhesion molecule 1 (CADM1) as a target gene of miR-148a using luciferase reporter assay. Both protein and mRNA levels of CADM1 were decreased in tissues from GBM patients. There was a strong negative correlation between exosomal miR-148a and CADM1 mRNA levels in samples of patients. Moreover, miR-148a antagonist increased p-STAT3 protein level to activate STAT3 pathway. In conclusion, our findings indicated that miR-148a delivered by exosomes may promote cancer cell proliferation and metastasis via targeting CADM1 to activate STAT3 pathway, suggesting a predictor and therapeutic target role of exosomal miR-148a in GBM patients.
引用
收藏
页码:643 / 651
页数:9
相关论文
共 33 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]
Mast cells modulate proliferation, migration and sternness of glioma cells through downregulation of GSK3β expression and inhibition of STAT3 activation [J].
Attarha, Sanaz ;
Roy, Ananya ;
Westermark, Bengt ;
Tchougounova, Elena .
CELLULAR SIGNALLING, 2017, 37 :81-92
[3]
Down-Regulation of Stat3 Decreases Invasion Activity and Induces Apoptosis of Human Glioma Cells [J].
Chen, Fuxue ;
Xu, Yaming ;
Luo, Youqun ;
Zheng, Da ;
Song, Yichao ;
Yu, Kangkang ;
Li, Hong ;
Zhang, Li ;
Zhong, Weiwei ;
Ji, Yonghua .
JOURNAL OF MOLECULAR NEUROSCIENCE, 2010, 40 (03) :353-359
[4]
MiR-148a increases glioma cell migration and invasion by downregulating GADD45A in human gliomas with IDH1 R132H mutations [J].
Cui, Daming ;
Sajan, Pandey ;
Shi, Jinlong ;
Shen, Yiwen ;
Wang, Ke ;
Deng, Xianyu ;
Zhou, Lin ;
Hu, Pingping ;
Gao, Liang .
ONCOTARGET, 2017, 8 (15) :25345-25361
[5]
Metastasis: recent discoveries and novel treatment strategies [J].
Eccles, Suzanne A. ;
Welch, Danny R. .
LANCET, 2007, 369 (9574) :1742-1757
[6]
Extracellular vesicle transfer of cancer pathogenic components [J].
Fujita, Yu ;
Yoshioka, Yusuke ;
Ochiya, Takahiro .
CANCER SCIENCE, 2016, 107 (04) :385-390
[7]
TGFβ-Responsive HMOX1 Expression Is Associated with Stemness and Invasion in Glioblastoma Multiforme [J].
Ghosh, Dhiman ;
Ulasov, Ilya V. ;
Chen, Liping ;
Harkins, Lualhati E. ;
Wallenborg, Karolina ;
Hothi, Parvinder ;
Rostad, Steven ;
Hood, Leroy ;
Cobbs, Charles S. .
STEM CELLS, 2016, 34 (09) :2276-2289
[8]
The emergent role of exosomes in glioma [J].
Gourlay, J. ;
Morokoff, A. P. ;
Luwor, R. B. ;
Zhu, H. J. ;
Kaye, A. H. ;
Stylli, S. S. .
JOURNAL OF CLINICAL NEUROSCIENCE, 2017, 35 :13-23
[9]
Exosomes Released by Melanoma Cells Prepare Sentinel Lymph Nodes for Tumor Metastasis [J].
Hood, Joshua L. ;
Roman, Susana San ;
Wickline, Samuel A. .
CANCER RESEARCH, 2011, 71 (11) :3792-3801
[10]
CD44v6 Dependence of Premetastatic Niche Preparation by Exosomes [J].
Jung, Thorsten ;
Castellana, Donatello ;
Klingbeil, Pamela ;
Hernandez, Ines Cuesta ;
Vitacolonna, Mario ;
Orlicky, David J. ;
Roffler, Steve ;
Brodt, Pnina ;
Zoeller, Margot .
NEOPLASIA, 2009, 11 (10) :1093-U150