Study links METTL3 to DNMT1 protein levels in high-grade serous ovarian cancer
Authors report that m6A modification by METTL3 enhances DNMT1 translation and silences tumor suppressor genes. Both are proposed as therapeutic targets in HGSC.
Researchers reported in Science Advances that the RNA methyltransferase METTL3 and the N6-methyladenosine (m6A) RNA modification pathway play an oncogenic role in high-grade serous carcinoma (HGSC), the most lethal subtype of ovarian cancer. science.org
Science Advancesscience.orgOpen source ↗ The disease is often diagnosed at advanced stages because it progresses without symptoms and has no early detection markers.
Depletion of METTL3 or its binding partner METTL14 impaired proliferation of ovarian cancer cells and tumor progression. According to the authors, m6A deposition enhances translation of the DNA methyltransferase DNMT1, an epigenetic repressor that silences tumor suppressor genes.
Pharmacologic inhibition of DNMT1 led to DNA hypomethylation and higher expression of the tumor suppressors TNFAIP3 and FBXO32. METTL3 depletion also increased expression of these genes. The authors propose that METTL3 sustains tumor growth by maintaining DNMT1 protein levels and repressing anti-tumor pathways, and they regard METTL3-mediated RNA modifications and DNMT1 as potential therapeutic targets in HGSC.
