METTL3 and DNMT1 in high-grade serous ovarian cancer

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. doi.org The disease is often diagnosed at advanced stages because it progresses without symptoms and has no early detection markers. doi.org

Depletion of METTL3 or its binding partner METTL14 impaired proliferation of ovarian cancer cells and tumor progression. doi.org According to the authors, m6A deposition enhances translation of the DNA methyltransferase DNMT1, an epigenetic repressor that silences tumor suppressor genes. doi.org

Pharmacologic inhibition of DNMT1 led to DNA hypomethylation and higher expression of the tumor suppressors TNFAIP3 and FBXO32. doi.org 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. doi.org

Study links METTL3 to DNMT1 protein levels in high-grade serous ovarian cancer

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