The inhibitory effect of melatonin on cancer cell dissemination is well established, yet the functional involvement of lncRNAs in melatonin signaling remains poorly understood. In this study, we identified a melatonin-attenuated lncRNA acting as a potential melatonin-regulated oral cancer stimulator (MROS-1). Downregulation of MROS-1 by melatonin suppressed TPA-induced oral cancer migration through replenishing the protein expression of prune homolog 2 (PRUNE2), which functioned as a tumor suppressor in oral cancer. Melatonin-mediated MROS-1/PRUNE2 expression and cell motility in oral cancer were regulated largely through the activation of JAK-STAT pathway. In addition, MROS-1, preferentially localized in the nuclei, promoted oral cancer migration in an epigenetic mechanism in which it modulates PRUNE2 expression by interacting with a member of the DNA methylation machinery, DNA methyltransferase 3A (DNMT3A). Higher methylation levels of PRUNE2 promoter were associated with nodal metastases and inversely correlated with PRUNE2 expression in head and neck cancer. Collectively, these findings suggest that MROS-1, serving as a functional mediator of melatonin signaling, could predispose patients with oral cancer to metastasize and may be implicated as a potential target for antimetastatic therapies.

中文翻译：

---

一种新的褪黑激素调节的 lncRNA 通过补充 PRUNE2 表达抑制 TPA 诱导的口腔癌细胞运动

褪黑激素对癌细胞传播的抑制作用已经确立，但 lncRNA 在褪黑激素信号传导中的功能参与仍然知之甚少。在这项研究中，我们鉴定了一种褪黑激素减毒的 lncRNA，它可以作为潜在的褪黑激素调节的口腔癌刺激物 (MROS-1)。褪黑激素对 MROS-1 的下调通过补充 prune 同源物 2 (PRUNE2) 的蛋白表达来抑制 TPA 诱导的口腔癌迁移，而 PRUNE2 在口腔癌中起到肿瘤抑制因子的作用。褪黑激素介导的口腔癌 MROS-1/PRUNE2 表达和细胞运动主要通过激活 JAK-STAT 通路进行调节。此外，优先定位于细胞核中的 MROS-1，在表观遗传机制中促进口腔癌迁移，其中它通过与 DNA 甲基化机制的成员 DNA 甲基转移酶 3A (DNMT3A) 相互作用来调节 PRUNE2 的表达。PRUNE2 启动子的较高甲基化水平与淋巴结转移相关，并且与头颈癌中 PRUNE2 的表达呈负相关。总的来说，这些发现表明，作为褪黑激素信号传导的功能介质的 MROS-1 可能使口腔癌患者易发生转移，并可能被认为是抗转移治疗的潜在靶点。