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Survival analysis showed that the patients in the high serum exosomal miR-1246 group had poorer overall survival and disease-free survival. Multivariate analysis showed that serum exosomal miR-1246 level was an independent prognostic factor for NSCLC. In conclusion, serum exosomal miR-1246 might be a useful diagnostic and prognostic biomarker for NSCLC.Our previous research confirmed the repression of SMADs signaling pathway inhibits the invasion, migration, and EMT in breast cancer MCF-7 and SKBR-3 cell lines by DNMT1 up-regulating CLD