Sun Xiaoxiao, Huang Xuan, Liu Li, Shen Weihong, Zheng Feifei, Liu Min, Sun Chengwen
The Department of Laboratory Medicine, Affiliated Hospital of Jiangnan University, Wuxi, China.
The Department of Imaging, Affiliated Hospital of Jiangnan University, Wuxi, China.
Transl Androl Urol. 2024 Nov 30;13(11):2358-2375. doi: 10.21037/tau-24-276. Epub 2024 Nov 28.
Prostate cancer (PCa) is the most prevalent adult malignancies worldwide and studies have shown that circular RNAs (circRNAs) play critical roles in the development and progression of PCa. As the most abundant modification, N6-methyladenosine (m6A) modification functions in regulating circRNAs expression and has been shown to regulate PCa progression. However, the biological relevance of m6A modification of circRNAs in PCa remains unclear. In addition, curcumin is reported to inhibit a variety of cancer cells while the biological functions in PCa have not yet been fully elucidated. Thus, our study aims to investigate whether curcumin can suppress PCa progression through the m6A-modified circRNAs.
By conducting m6A methylation immunoprecipitation combined with quantitative real-time polymerase chain reaction (MeRIP-qPCR) assay, cell counting kit-8 (CCK-8) assay and wound healing assay, increased m6A modification on circ0030568 was detected and upregulated circ0030568 was also observed in different PCa cells lines, which promotes proliferation and migration of PCa cells.
More importantly, the results confirmed that curcumin could suppress the proliferation and migration of PCa cells lines by inhibiting METTL3-modified circ0030568. Mechanistically, m6A reader YTHDF2 elevated the stability of circ0030568 via m6A modification and curcumin could suppress PCa progression by inhibiting YTHDF2 mediated circ0030568 stability.
Taken together, circ0030568 may act as a promising biomarker and an attractive target for PCa treatment and curcumin's inhibition of m6A-modified circ0030568 may be a potential mechanism of its anti-PCa.
前列腺癌（PCa）是全球最常见的成人恶性肿瘤，研究表明环状RNA（circRNAs）在PCa的发生和发展中起关键作用。作为最丰富的修饰，N6-甲基腺苷（m6A）修饰在调节circRNAs表达中起作用，并已被证明可调节PCa的进展。然而，circRNAs的m6A修饰在PCa中的生物学相关性仍不清楚。此外，姜黄素据报道可抑制多种癌细胞，但其在PCa中的生物学功能尚未完全阐明。因此，我们的研究旨在探讨姜黄素是否能通过m6A修饰的circRNAs抑制PCa的进展。
通过进行m6A甲基化免疫沉淀结合定量实时聚合酶链反应（MeRIP-qPCR）分析、细胞计数试剂盒-8（CCK-8）分析和伤口愈合分析，检测到circ0030568上m6A修饰增加，并且在不同的PCa细胞系中也观察到circ0030568上调，其促进PCa细胞的增殖和迁移。
更重要的是，结果证实姜黄素可通过抑制METTL3修饰的circ0030568来抑制PCa细胞系的增殖和迁移。机制上，m6A阅读器YTHDF2通过m6A修饰提高了circ0030568的稳定性，而姜黄素可通过抑制YTHDF2介导的circ0030568稳定性来抑制PCa进展。
综上所述，circ0030568可能是一种有前景的生物标志物和PCa治疗的有吸引力的靶点，姜黄素对m6A修饰的circ0030568的抑制作用可能是其抗PCa的潜在机制。
