Exosomal hsa_circ_0000519 modulates the NSCLC cell growth and metastasis via miR-1258/RHOV axis

Abstract

This study aims to explore the function and mechanism of exosomal circ_0000519 in non-small cell lung cancer (NSCLC) development. Expression of circ_0000519, microRNA (miR)-1258, and Ras homolog gene family V (RHOV) in serum samples of NSCLC patients or cell lines were examined via quantitative reverse transcription-polymerase chain reaction and Western blotting. The function of circ_0000519 was evaluated through 5-ethynyl-2′-deoxyuridine (EdU) staining, colony formation, transwell, Western blotting, xenograft, and immunohistochemistry analyses. The binding relationship was evaluated by a dual-luciferase reporter assay and RNA pull-down assay. Results showed that circ_0000519 abundance was enhanced in the serum samples of NSCLC patients and cells. circ_0000519 knockdown suppressed the cell growth by decreasing the colony-formation ability and Cyclin D1 expression and inhibited cell metastasis via reducing migration, invasion, and levels of Vimentin and matrix metalloproteinase 9 (MMP9). circ_0000519 overexpression promoted cell growth and metastasis. circ_0000519 was carried by exosomes and knockdown of exosomal circ_0000519 suppressed the cell growth and metastasis. miR-1258 was downregulated in NSCLC cells and targeted by circ_0000519. RHOV was targeted by miR-1258 and upregulated in the NSCLC cells. miR-1258 knockdown or RHOV overexpression attenuated the influence of exosomal circ_0000519 knockdown on cell growth and metastasis. Exosomal circ_0000519 knockdown decreased xenograft tumor growth. Collectively, the knockdown of exosomal circ_0000519 repressed the cell growth and metastasis in NSCLC through the miR-1258/RHOV axis, which provided a new insight into NSCLC development and treatment.

Keywords

• non-small cell lung cancer
• exosome
• hsa_circ_0000519
• mir-1258
• rhov