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

富含 miR-224-5p 的外泌体通过直接靶向非小细胞肺癌中的雄激素受体促进肿瘤发生

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作者:Jinbao Zhou, Hongshu Wang, Qiangling Sun, Xiaomin Liu, Zong Wu, Xianyi Wang, Wentao Fang, Zhongliang Ma

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.

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