Exosomal miR-196a-1 Promotes Gastric Cancer Cell Invasion and Metastasis By Targeting SFRP1

Abstract

Aim: To investigate the role of exosomal miRNAs on gastric cancer (GC) metastasis. Materials & methods: miRNA expression profiles of exosomes with distinct invasion potentials were analyzed using miRNA microarray and validated by quantitative real-time PCR. In vitro and in vivo experiments assessed the role of exosomal miR-196a-1 in GC's metastasis. Results: High expression level of exosomal miR-196a-1 expression was significantly associated with poor survival in GC. Exosomes that contained miR-196a-1 were secreted from high-invasive GC cells. Ectopic miR-196a-1 expression promoted invasion of low-invasive GC cells by targeting SFRP1. Conclusion: miR-196a-1 was delivered from high-invasive GC into low-invasive GC cells via exosomes and promoted metastasis to the liver in vitro and in vivo.

Keywords:

• exosome
• gastric cancer
• invasion
• metastasis
• miR-196a-1
• SFRP1

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at:www.tandfonline.com/doi/full/10.2217/epi-2016-0184

Author contributions

G Xu, H Xia and W Zhang designed and supervised the experiments. C Feng, J She and X Chen performed experiments. X Zhang and Q Zhang performed the biostatistical analyses. J Ye, J Shi, J Tao, M Feng and W Guan enrolled patients and provided patient samples. Y Wang performed electron microscopy imaging. C Feng and Y Wang wrote the manuscript. All authors have revised the final version.

Financial & competing interests disclosure

This work was supported by grants from the National Natural Science Foundation of China (Grant Nos. 81201909, 81472714, 81572338 and 81672380) and the Nanjing Medical Science and Technology Development Program (Nos. YKK15061, YKK16108 and YKK16078). This work was also part of a C-class sponsored research project of the Jiangsu Provincial Six Talent Peaks (WSN-078). This paper was supported by Major science and technology and Medical science and technology research grants of He’nan Province (No.161100311400, No.201502027), and also supported by the project of National Young 1000 Talents Program of China and Jiangsu Province Education Department Grant (KY216R201601). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing support was provided by Enago and was funded by the above funding sources.

Ethical conduct of research

All experimental procedures were performed in accordance with protocols approved by the Institutional Animal Care and Research Advisory Committee of the First Affiliated Hospital of Nanjing Medical University Nanjing and Henan Cancer Hospital. The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Data sharing statement

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.