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Background  Early diagnosis improves the prognosis for non‐small cell lung cancer (NSCLC); therefore, there is a pressing need for effective diagnostic methods for NSCLC. Increasing evidence indicates that serum exosomal micro RNAs (miRNAs) represent promising diagnostic and prognostic markers for multiple cancers. Here, we explored a panel of miRNAs for NSCLC diagnosis and functionally characterized miR‐1269a in the pathogenesis of NSCLC.   Methods:  First, we analyzed high‐throughput data from The Cancer Genome Atlas (TCGA) to identify differentially expressed miRNAs between NSCLC patients and healthy controls. We examined the expression profiles of the identified miRNAs using qRT‐PCR.   Results:  We found that four micro‐RNAs (hsa‐miR‐9‐3p, hsa‐miR‐205‐5p, hsa‐miR‐210‐5p, and hsa‐miR‐1269a) were more abundant in serum exosomes from NSCLC patients. A logistic regression model validated the diagnostic efficacy of the four‐microRNA panel, allowing us to distinguish NSCLC patients from healthy controls with AUCs of 0.915 and 0.878 for the training and validation sets, respectively. Functionally, NSCLC cell proliferation, migration, and invasion were affected by the aberrant expression of hsa‐miR‐1269a in culture. Reduced expression of miR‐1269a resulted in reduced proliferation, migration, and invasion through targeting the forkhead box O1 gene ( FOXO1 ).   Conclusions:  Taken together, our study identified a panel of four serum exosomal miRNAs as a potential noninvasive diagnostic biomarker for NSCLC. The interactions between  FOXO1  and miR‐1269a represent novel potential targets for NSCLC therapy.

Serum exosomal miR ‐1269a serves as a diagnostic marker and plays an oncogenic role in non‐small cell lung cancer