Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou 510632, Guangdong Province, China.
Aging (Albany NY). 2021 Jan 10;13(3):4045-4062. doi: 10.18632/aging.202371.
In this study, we found that ALKBH5, a key component of the -methyladenosine (mA) methyltransferase complex, was significantly elevated in uveal melanoma (UM) cell lines and that ALKBH5 downregulation inhibited tumor growth . High ALKBH5 expression predicted worse outcome in patients with UM. EP300-induced H3K27 acetylation activation increased ALKBH5 expression. Downregulation of ALKBH5 inhibited UM cell proliferation, migration, and invasion and increased apoptosis . Besides, ALKBH5 may promote UM metastasis by inducing epithelial-to-mesenchymal transition (EMT) via demethylation of mRNA, which increases its expression and stability. In sum, our study indicates that AKLBH5-induced mA demethylation of mRNA promotes UM progression. Therefore, AKLBH5 is a potential prognostic biomarker and therapeutic target in UM.
在这项研究中，我们发现 ALKBH5，一种 mA 甲基转移酶复合物的关键组成部分，在葡萄膜黑色素瘤（UM）细胞系中显著升高，并且 ALKBH5 的下调抑制了肿瘤的生长。ALKBH5 的高表达预示着 UM 患者预后不良。EP300 诱导的 H3K27 乙酰化激活增加了 ALKBH5 的表达。下调 ALKBH5 抑制了 UM 细胞的增殖、迁移和侵袭，并增加了细胞凋亡。此外，ALKBH5 可能通过去甲基化 mRNA 诱导上皮间质转化（EMT）来促进 UM 转移，从而增加其表达和稳定性。总之，我们的研究表明，AKLBH5 诱导的 mA 去甲基化促进了 UM 的进展。因此，AKLBH5 是 UM 中潜在的预后生物标志物和治疗靶点。
