Carboplatin Is Associated with Changes in Components of the m6A Machinery in Triple-Negative Breast Cancer Cells
Abstract
Triple-negative breast cancer (TNBC), a breast cancer subtype characterized by aggressiveness and high recurrence, is usually treated with chemotherapy agents, such as platinum-based drugs. Chemotherapy modulates gene and protein expression, including epitranscriptomic regulators such as components of the m6A methylosome. This study examined the effects of carboplatin (CP) on the expression of m6A methylosome machinery (METTL3, METTL14, WTAP, FTO, YTHDF2) and the m6A methylation mark in two cell lines (HCC1937 and MDA-MB-231). Using KM-plotter, a survival analysis was performed, while molecular docking and molecular dynamics (MD) simulations were conducted to identify critical structural interactions between CP and m6A methylosome components. Gene and protein expression analyses revealed that FTO was consistently downregulated after CP treatment in both cell lines. Bioinformatic survival analysis linked low FTO expression to improved patient survival, and in silico docking and MD simulations confirmed that FTO established the most stable interaction with CP. Conversely, METTL3 expression was decisive for the global m6A methylation mark, being upregulated in HCC1937 cells (increasing m6A marks) but downregulated in MDA-MB-231 cells (decreasing m6A marks), while high METTL3 transcripts correlated with better prognosis. Docking and MD insights suggested strong interactions between CP and FTO/METTL3 proteins. These findings indicate that CP influences m6A machinery in TNBC…
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