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miR-224-5p-enriched exosomes promote tumorigenesis by directly targeting androgen receptor in non-small cell lung cancer

miR-224-5p-enriched exosomes promote tumorigenesis by directly targeting androgen receptor in non-small cell lung cancer

Authors :
Xianyi Wang
Zong Wu
Qiangling Sun
Zhongliang Ma
Wentao Fang
Xiaomin Liu
Hongshu Wang
Jinbao Zhou
Source :
Molecular Therapy. Nucleic Acids, Molecular Therapy: Nucleic Acids, Vol 23, Iss, Pp 1217-1228 (2021)
Publication Year :
2021
Publisher :
American Society of Gene & Cell Therapy, 2021.

Abstract

Non-small cell lung cancer (NSCLC) is the most common form of cancer, resulting in cancer-related deaths worldwide. Exosomes, a subclass of extracellular vesicles, are produced and secreted from various types of cells, including cancer cells. Cancer-derived exosomes can deliver nucleic acids, proteins, and lipids to provide a favorable microenvironment that supports tumor growth through enhancing cell proliferation and metastasis. Our results showed that miR-224-5p was upregulated in NSCLC patient tissues and cell lines, with a tumor-promoting phenotype. Meanwhile, exosome-derived miR-224-5p induced cell proliferation and metastasis in NSCLC and human lung cells. Moreover, we characterized the androgen receptor (AR) as a direct target of miR-224-5p. Tumor xenograft assay experiments revealed that overexpression of miR-224-5p drove NSCLC tumor growth via the suppression of AR and the mediation of epithelial-mesenchymal transition (EMT). Collectively, our results suggest that miR-224-5p-enriched exosomes promote tumorigenesis by directly targeting AR in NSCLC, which may provide novel potential therapeutic and preventive targets for NSCLC.<br />Graphical Abstract<br />Exosomes and microRNAs play important roles in tumorigenesis. In non-small lung cancer, the cancer-derived exosome miR-224-5p increased significantly. With exosomes transporting, miR-224-5p promoted the proliferation and metastasis ability of their receptor cells via targeting androgenic receptor. Consequently, exosomal miR-224-5p may have a promising prospect in lung cancer therapy.

Details

Language :
English
ISSN :
21622531
Volume :
23
Database :
OpenAIRE
Journal :
Molecular Therapy. Nucleic Acids
Accession number :
edsair.doi.dedup.....cab691744e99623013d5e1f9f41f6584