Lung adenocarcinoma (LUAD) is a predominant type of lung cancer in never-smoker patients. In this study, we identified a long noncoding RNA (lncRNA) LINC00857 that might regulate radio-sensitivity of LUAD cells. Expression of LINC00857 and baculoviral IAP repeat containing 5 (BIRC5) was determined to be upregulated in LUAD cells and tissues using qRT-PCR and western blot analysis. The correlation between LINC00857 and nuclear factor kappa B subunit 1 (NF-kB1) was verified using RNA immunoprecipitation and chromatin immunoprecipitation assays, while the binding relationship between NF-kB1 and BIRC5 was determined by dualluciferase reporter assay. It was suggested that LINC00857 could recruit NF-kB1 in BIRC5 promoter region. BIRC5 promoter activity was repressed in response to small interfering-LINC00857 (si-LINC00857) in LUAD cells. Silencing LINC00857 or BIRC5 reduced proliferation and colony formation but enhanced apoptosis and radio-sensitivity of LUAD cells. The experiment in vivo verified the function of silencing LINC00857 on enhancing radio-sensitivity of LUAD cells. Our results reveal a functional regulatory LINC00857-NF-kB1-BIRC5 triplet in LUAD cells, suggesting LINC00857 as a potential target for LUAD treatment.

Lung adenocarcinoma (LUAD), as the most common subtype of non‐small cell lung cancer, is responsible for more than 500 000 deaths worldwide annually. In this study, we identify a novel microRNA‐26b‐5p (miR‐26b‐5p) and elucidated its function on LUAD. The survival rate of parent LUAD cells and radiation‐resistant LUAD cells were determined using clonogenic survival assay. We overexpressed or inhibited miR‐26b‐5p in LUAD, and the correlation between activating transcription factor 2 (ATF2) and miR‐26b‐5p was determined using integrated bioinformatics analysis and dual‐luciferase reporter gene assay. Exosomes derived from A549 cell lines were then detected using Western blot assay, followed by co‐transfection with radiation‐resistant A549R cells. LUAD tissues and serum were collected, followed by miR‐26b‐5p relative expression quantification using RT‐qPCR. miR‐26b‐5p was identified as the most differentially expressed miRNA and was down‐regulated in LUAD. Radiation‐resistant cells were more resistant to X‐radiation compared with parent cells. miR‐26b‐5p overexpression and X‐irradiation led to enhanced radiosensitivity of LUAD cells. ATF2 was negatively targeted by miR‐26b‐5p. Exosomal miR‐26b‐5p derived from A549 cells could be transported to irradiation‐resistant LUAD cells and inhibit ATF2 expression to promote DNA damage, apoptosis and radiosensitivity of LUAD cells, which was verified using serum‐based miR‐26b‐5p. Our results show a regulatory network of miR‐26b‐5p on radiosensitivity of LUAD cells, which may serve as a non‐invasive biomarker for LUAD.