期刊
EXPERIMENTAL CELL RESEARCH
卷 379, 期 2, 页码 203-213出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2019.03.035
关键词
Exosome; miR499a; mTOR pathway; Lung cancer
资金
- National Key R&D Program of China [2016YFC1303300]
- National Natural Science Foundation of China [81672272, 81773115]
- National Key Grant of China [2016YFC0906400]
- Key Project of Shanghai Health & Family Planning Commission [201540365]
- Shanghai Municipal Science & Technology Commission Research Project [17431906103]
- Shanghai Scientific Research Projects [14140902800]
Tumor-derived exosomes contain informative microRNAs involved in carcinogenesis, cell migration, invasion and epithelial-mesenchymal transition (EMT), eventually contributing to metastasis of cancers. This study aims to clarify which and how exosomal miRNA affects tumor carcinogenesis and metastasis. Among them, miR-499a-5p was upregulated in both highly metastatic lung cancer cell line and their exosomes. MiR-499a-5p over-expression promoted cell proliferation, migration and EMT, while miR-499a-5p knockdown suppressed these processes in vitro. Inhibition of miR-499a-5p by antagomirs administration restrained tumor growth in vivo. Consequently, miR499a-sufficient exosomes, derived from highly metastatic cell line, enhanced cell proliferation, migration and EMT via mTOR pathway, and the effect could be inhibited by miR-499a-5p inhibitor. The study reveals the potential diagnostic and therapeutic value of cancer-derived exosomal miR-499a-5p, and sheds a new insight on a novel molecular mechanism which modulates metastasis.
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