To exclude the potential off-target effects, we performed shRNA knockdown assay against PRPS2 in H1299 cell line with low endogenous PRPS2 expression level instead, and the results suggested that knockdown of PRPS2 H1299 cell line does not interfere the cell proliferation, confirming that PRPS2 is indeed on-target and dependency in cell lines with high endogenous PRPS2 expression level, such as NSCLC (Supplementary Fig. 15). Here, PRPS2 is linked to non-small cell lung carcinoma.