Fig. 1.

METTL17 expression is positively correlated with ferroptosis-resistance of cancer cells and knockdown of METTL17 sensitizes CRC cells to ferroptosis.

A. METTL17 expression exhibited positive correlation with resistance to GPX4 inhibitors (ML162 and RSL3) in cancer cells. Data in plots were mined from the CTRP database and each plot represented a certain anti-tumor compound.

B and C. Scatter plots showing the correlation between ML162 (B), RSL3 (C) AUC drug sensitivity and METTL17 protein level in colorectal cancer or other cancer cell lines. Data were mined from the DepMap database and each plot represented a certain cancer cell line.

D and E. Cell viability of control (Scramble) and METTL17 knockdown (shM17#3 and shM17#5) SW620 cells (D) or RKO cells (E) treated with ML162 or RSL3 for 4 h after pretreatment with or without DFO (100 μM) for 1 h n = 3–4 per group.

F. Microscopy showing cell death. SW620 cells were treated with ML162 (10 μM) for 4 h following pretreatment with or without DFO (100 μM) for 1 h. Upper panel: propidium iodide (PI) staining for dead cells; middle panel, phase-contrast; lower panel: merge image. Scale bar = 200 μm.

G and H. Quantification of ferroptotic cells determined by PI-positive staining in SW620 cells (G) or RKO cells (H) treated with ML162 (10 μM) or RSL3 (10 μM) for 4 h following pretreatment with or without DFO (100 μM) for 1 h. The number of cell deaths was counted from Fig. 1F and Supplementary Fig. 1 n = 3 per group.

Data are shown as mean ± SD. ^##p < 0.01, ^###p < 0.001 compared to ML162 or RSL3-treated Scramble group, and **p < 0.01, ***p < 0.001 compared with the indicated two groups, based on two-sided Student's t-test or Pearson r test.