Aging-US: Demethylation of FOXM1 mRNA promotes progression of uveal melanoma09-08-2021
Aging-US published a Special Collection on Eye Disease which included "ALKBH5-mediated m6A demethylation of FOXM1 mRNA promotes progression of uveal melanoma" which reported that ALKBH5, a key component of the N6-methyladenosine (m6A) methyltransferase complex, was significantly elevated in uveal melanoma cell lines and inhibited tumor growth in vitro and in vivo.
EP300-induced H3K27 acetylation activation activated increased ALkbH5 expression and inhibited UM cell proliferation, migration, invasion and increased apoptosis in vitro. Besides, it may promote UM metastasis by inducing epithelial-to-mesenchymal transition (EMT) via demethylation of FOXM1 mRNA, which increases its expression and stability. It is a potential prognostic biomarker and therapeutic target in UM.
Dr. Jingxiang Zhong and Dr. Lian Liu said, "Uveal melanoma (UM), which originates from melanocytes, is the most common primary intraocular malignancy in adults."
Up to 50% of patients with primary malignant meningitis (UM) will develop metastatic disease.
The most common sites of UM metastasis are the liver (60.5%), lungs (24.4%), skin/soft tissue (10.9%), and bone (8.4%). Unfortunately, the 1-year survival rate of UM patients with metastases is only 15% . There is a pressing need to find useful prognostic biomarkers and therapeutic targets for this disease. Alkhabh5 overexpression of ALKBH5 promotes EMT of UM by upregulating FOXM1 expression via demethylating the m6A modification and further increasing the stability of FOXm1 mRNA.
Figure 7. The graphic illustration of ALKBH5-mediated m6A demethylation of FOXM1 mRNA promotes progression of uveal melanoma.
The Zhong/Liu Research Team concluded in their Aging-US Research Output, "we demonstrate that ALKBH5, which is positively regulated by epigenetic modifications of H3K27 acetylation, promotes tumor progression by inducing tumor EMT and increasing FOXM1 expression via m6A demethylation (Figure 7). Therefore, ALKBH5 is a potential target of UM molecular therapy."
Full Text - https://www.aging-us.com/article/202371/text
Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways.