Transgenic construction and functional miRNA analysis identify the role of miR-7 in prostate cancer suppression.

ABSTRACT

Although miR-7 suppresses the initiation and progression in cancers, little is known about its role in prostate cancer, especially in transgenic mouse models. In present study, we found that expression of miR-7, regulated by p53, was lower in prostate cancer tissues, and miR-7 overexpression significantly mitigated prostate cancer cells growth both in vitro, in organoids and in vivo regardless of p53 status. After we generated miR-7 overexpression transgenic mice and miR-7+/TRAMP mice, we found that transgenic overexpression of miR-7 in mice is safe and miR-7+/TRAMP mice have a preferred overall survival. Moreover, in vivo treatment of miR-7 inhibited subcutaneous tumour growth in mice and prolonged the survival of mice harboring prostate cancer lung metastasis when co-injection with PD-1 antibody. In addition, miR-7 downregulated glycolysis of prostate cancer cells by inhibiting several key pathways including HIF-1α, and subsequently remodeled acidic tumour microenvironment, PanKLa level and T cell infiltration. In summary, our findings highlighted a promising target for development of miRNA-based therapeutics for prostate cancer patients regardless of p53 status.