Sulforaphane inhibits the growth of prostate cancer by regulating the microRNA-3919/DJ-1 axis

Fangxi Zhang; Xiaofeng Wan; Jianmin Zhan; Ming Shen; Runsheng Li

doi:10.3389/fonc.2024.1361152

Sulforaphane inhibits the growth of prostate cancer by regulating the microRNA-3919/DJ-1 axis

Front Oncol. 2024 Mar 7:14:1361152. doi: 10.3389/fonc.2024.1361152. eCollection 2024.

Authors

Fangxi Zhang^{1

2}, Xiaofeng Wan¹, Jianmin Zhan¹, Ming Shen¹, Runsheng Li¹

Affiliations

¹ National Health Commission (NHC) Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), School of Pharmacy, Fudan University, Shanghai, China.
² Department of Pharmacy and Examination, Heze Medical Collge, Heze, China.

Abstract

Background: Prostate cancer (PCa) is the second most common solid cancer among men worldwide and the fifth leading cause of cancer-related deaths in men. Sulforaphane (SFN), an isothiocyanate compound, has been shown to exert inhibitory effects on a variety of cancers. However, the biological function of SFN in PCa has not been fully elucidated. The objective of this study was conducted to further investigate the possible underlying mechanism of SFN in PCa using in vitro cell culture and in vivo tumor model experiments.

Methods: Cell viability, migration, invasion, and apoptosis were analyzed by Cell Counting Kit-8 (CCK-8), wound healing assay, transwell assay, or flow cytometry. Expression of microRNA (miR)-3919 was detected by quantitative real-time polymerase chain reaction (qRT-PCR) or in situ hybridization assay. Xenograft assay was conducted to validated the antitumor effect of miR-3919. The targeting relationship between miR-3919 and DJ-1 was verified by dual-luciferase reporter assay. The level of DJ-1was measured by qRT-PCR or western blotting (WB).

Results: In the present study, SFN downregulated mRNA and protein expression of DJ-1, an oncogenic gene. Small RNA sequencing analysis and dual-luciferase reporter assay confirmed that microRNA (miR)-3919 directly targeted DJ-1 to inhibition its expression. Furthermore, miR-3919 overexpression impeded viability, migration, and invasion and promoted apoptosis of PCa cells. Tumor growth in nude mice was also inhibited by miR-3919 overexpression, and miR-3919 expression in PCa tissues was lower than that in peritumoral tissues in an in situ hybridization assay. Transfection with miR-3919 inhibitors partially reversed the effects of SFN on cell viability, migration, invasion, and apoptosis.

Conclusion: Overall, the miR-3919/DJ-1 axis may be involved in the effects of SFN on the malignant biological behavior of PCa cells, which might be a new therapeutic target in PCa.

Keywords: DJ-1; microRNA-3919; prostate cancer; signal pathway; sulforaphane.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The work was supported by the National Natural Science Foundation of China (No. 82172753, 81971443 and 82271640), Natural Science Foundation of Shanghai (No. 21ZR1454800, 21140903600, 21S11901000).