In this study, we found that ALKBH5, a key component of the N 6 -methyladenosine (m 6 A) methyltransferase complex, was significantly elevated in uveal melanoma (UM) cell lines and that ALKBH5 downregulation inhibited tumor growth in vivo . 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 in vitro . Besides, ALKBH5 may promote UM metastasis by inducing epithelial-to-mesenchymal transition (EMT) via demethylation of FOXM1 mRNA, which increases its expression and stability. In sum, our study indicates that AKLBH5-induced m 6 A demethylation of FOXM1 mRNA promotes UM progression. Therefore, AKLBH5 is a potential prognostic biomarker and therapeutic target in UM.

Introduction The loss of retinal pigment epithelial (RPE) cells is associated with the etiology of diabetic retinopathy (DR). This study investigated the effects of circular RNA ZNF532 (circZNF532) on apoptosis and pyroptosis of RPE cells. Materials and Methods Blood samples were collected from patients with DR and healthy volunteers. A human RPE cell line ARPE‐19 was induced by high glucose (HG) and assayed for cell viability, apoptosis, and pyroptosis. The binding of miR‐20b‐5p with circZNF532 and STAT3 was confirmed by a luciferase activity assay. A mouse model of diabetic retinopathy was established. Results CircZNF532 and STAT3 were upregulated but miR‐20b‐5p was downregulated in the serum samples of patients with DR and HG‐induced ARPE‐19 cells. Elevated miR‐20b‐5p or CircZNF532 knockdown enhanced proliferation but reduced apoptosis and pyroptosis of ARPE‐19 cells. CircZNF532 sponged miR‐20b‐5p and inhibited its expression. STAT3 was verified as a target of miR‐20b‐5p. MiR‐20b‐5p modulated ARPE‐19 cell viability, apoptosis, and pyroptosis by targeting STAT3. Mice with STZ‐induced diabetes showed elevated expressions of circZNF532 and STAT3 but decreased the level of miR‐20b‐5p compared with the controls. Knockdown of circZNF532 inhibited apoptosis and pyroptosis in mouse retinal tissues. Conclusion CircZNF532 knockdown rescued human RPE cells from HG‐induced apoptosis and pyroptosis by regulating STAT3 via miR‐20b‐5p.

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The activation and proliferation of human Tenon's fibroblasts (HTFs) play a vital role in the fibrosis in the pathology of the scar formation after the glaucoma filtration surgery. Transforming growth factor β1 (TGFβ1)/Smads signaling has been reported to promote fibrosis. In our previous study, we revealed that TGFβ1‐induced orbital fibroblast activation and proliferation through Wnt/β‐catenin signaling. As microRNA (miR)‐139 could target several factors in Wnt signaling to modulate fibrosis, here, the effect and mechanism of miR‐139 in HTF activation and proliferation were investigated. miR‐139 overexpression significantly reversed the TGFβ1‐induced increase in collagen I and α‐smooth muscle actin contents and proliferation in HTFs. CTNNB1 and CTNND1 were direct downstream of miR‐139 and can significantly restore the suppressive effect of miR‐139 on the activation and proliferation in HTFs under TGFβ1 stimulation. Smad2/3/4 complex inhibits the transcription activity of miR‐139, most possibly by Smad4 binding to the miR‐139 promoter. Taken together, we demonstrated a new mechanism of HTF activation and proliferation from the perspective of miRNA regulation, which may provide new strategies for improving the fibrosis after the glaucoma filtration surgery.