背景:硒与癌症之间的有趣联系类似于一个令人着迷的难题,使研究人员保持参与和好奇。虽然硒已显示出通过补充减少癌症风险的希望,它与宫颈癌中的表观遗传学的相互作用仍然是一个令人着迷但尚未探索的领域。解开硒的作用及其与表观遗传因素的相互作用的复杂性,可以在对抗这种复杂疾病的斗争中开启有价值的见解。
结果:硒以各种方式对宫颈癌细胞显示出显着的抑制作用。在体外研究中,它有效地抑制了增殖,迁移,和宫颈癌细胞的侵袭,同时促进细胞凋亡。硒还显示出对人类宫颈癌衍生的类器官的显着抑制作用。此外,在一项体内研究中,二氧化硒溶液的给药有效抑制小鼠宫颈癌肿瘤的生长。硒的抑制作用背后的机制之一是其抑制组蛋白脱甲基酶的能力,特别是JMJD3和UTX。在体外和体内都观察到这种抑制。值得注意的是,当JMJD3和UTX被GSK-J4抑制时,在体外和体内模型中都观察到类似的生物学效应,有效抑制源自宫颈癌患者的类器官模型。抑制JMJD3和UTX也诱导G2/M期停滞,促进细胞凋亡,并逆转上皮-间质转化(EMT)。ChIP-qPCR分析证实,JMJD3和UTX抑制增加了特定组蛋白修饰的募集,H3K27me3,到宫颈癌细胞(HeLa和SiHa细胞)中靶基因的转录起始位点(TSS)。此外,发现JMJD3和UTX在宫颈癌组织中的表达显著高于癌旁正常宫颈组织,表明它们作为治疗靶点的潜力。
结论:我们的研究强调了硒对生长的显着抑制作用,迁移,和宫颈癌细胞的侵袭,促进细胞凋亡并显示出作为治疗剂的有希望的潜力。我们确定了组蛋白去甲基化酶JMJD3和UTX作为硒的特异性靶标,它们的抑制作用复制了观察到的对癌细胞行为的影响。这些发现表明,JMJD3和UTX可能是基于硒的宫颈癌治疗的有价值的靶标。
BACKGROUND: The intriguing connection between selenium and cancer resembles a captivating puzzle that keeps researchers engaged and curious. While selenium has shown promise in reducing cancer risks through supplementation, its interaction with epigenetics in cervical cancer remains a fascinating yet largely unexplored realm. Unraveling the intricacies of selenium\'s role and its interaction with epigenetic factors could unlock valuable insights in the battle against this complex disease.
RESULTS: Selenium has shown remarkable inhibitory effects on cervical cancer cells in various ways. In in vitro studies, it effectively inhibits the proliferation, migration, and invasion of cervical cancer cells, while promoting apoptosis. Selenium also demonstrates significant inhibitory effects on human cervical cancer-derived organoids. Furthermore, in an in vivo study, the administration of selenium dioxide solution effectively suppresses the growth of cervical cancer tumors in mice. One of the mechanisms behind selenium\'s inhibitory effects is its ability to inhibit histone demethylases, specifically JMJD3 and UTX. This inhibition is observed both in vitro and in vivo. Notably, when JMJD3 and UTX are inhibited with GSK-J4, similar biological effects are observed in both in vitro and in vivo models, effectively inhibiting organoid models derived from cervical cancer patients. Inhibiting JMJD3 and UTX also induces G2/M phase arrest, promotes cellular apoptosis, and reverses epithelial-mesenchymal transition (EMT). ChIP-qPCR analysis confirms that JMJD3 and UTX inhibition increases the recruitment of a specific histone modification, H3K27me3, to the transcription start sites (TSS) of target genes in cervical cancer cells (HeLa and SiHa cells). Furthermore, the expressions of JMJD3 and UTX are found to be significantly higher in cervical cancer tissues compared to adjacent normal cervical tissues, suggesting their potential as therapeutic targets.
CONCLUSIONS: Our study highlights the significant inhibitory effects of selenium on the growth, migration, and invasion of cervical cancer cells, promoting apoptosis and displaying promising potential as a therapeutic agent. We identified the histone demethylases JMJD3 and UTX as specific targets of selenium, and their inhibition replicates the observed effects on cancer cell behavior. These findings suggest that JMJD3 and UTX could be valuable targets for selenium-based treatments of cervical cancer.