期刊
ONCOGENE
卷 41, 期 41, 页码 4645-4657出版社
SPRINGERNATURE
DOI: 10.1038/s41388-022-02461-0
关键词
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资金
- National Natural Science Foundation of China [81872089, 81672551, 82102799]
- Natural Science Foundation of Jiangsu Province [BK20210230]
- Key Research and Development Program of Jiangsu Province [BE2019751]
- Jiangsu Provincial Medical Talent [ZDRCA2016080]
- Jiangsu Provincial Medical Innovation Team [CXTDA2017025]
- Doctor of Entrepreneurship and Innovation in Jiangsu Province [JSSCBS20210138, JSSCBS20210088]
- General Project of Medical Research of Jiangsu Health and Wellness Committee [M2020049]
- Key R&D (Social Development) Projects of Jiangsu Province [BE2018629]
- Wuxi Taihu Talents Program Medical and Health High-level Talents Project, First Affiliated Hospital of Bengbu Medical College Science Fund for Outstanding Young Scholars [2019BYYFYYQ09]
This study found that overexpression of miR-7 can suppress tumor growth and prolong survival in transgenic mouse models of prostate cancer. miR-7 inhibits glycolysis in prostate cancer cells by regulating multiple key pathways and remodels the acidic tumor microenvironment. These findings provide hope for using miR-7 as a target for treating prostate cancer.
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-1 alpha, 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.
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