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

Jinbao Zhou; Hongshu Wang; Qiangling Sun; Xiaomin Liu; Zong Wu; Xianyi Wang; Wentao Fang; Zhongliang Ma

doi:10.1016/j.omtn.2021.01.028

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

Mol Ther Nucleic Acids. 2021 Feb 3:23:1217-1228. doi: 10.1016/j.omtn.2021.01.028. eCollection 2021 Mar 5.

Authors

Jinbao Zhou¹, Hongshu Wang², Qiangling Sun³, Xiaomin Liu¹, Zong Wu¹, Xianyi Wang¹, Wentao Fang³, Zhongliang Ma¹

Affiliations

¹ Lab for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai 200444, China.
² Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
³ Department of Thoracic Surgery, Thoracic Cancer Institute, Shanghai Chest Hospital, Jiaotong University Medical School, Shanghai 200030, China.

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.

Keywords: AR; Exosome; NSCLC; Tumorigenesis; miR-224-5p.