The same downregulation of CCNE1 was also apparent in SIRT7 KD ARF-positive Calu-3 lung cancer cells (SI Appendix, Fig. S4D) and importantly in lungs of SIRT7-mutant mice, demonstrating the physiological relevance of this phenomenon (SI Appendix, Fig. S4E). This evidence concerns the gene CDKN2A and lung carcinoma.