LAUSR

Non‐small cell lung cancer (NSCLC) is a major type of lung cancer. Drug resistance is a enormous obstacle for cancer treatment. Copious microRNAs (miRNAs) have been demonstrated to be implicated in drug resistance in NSCLC. In the present study, RT‐qPCR assay revealed that microRNA‐1 (miR‐1) expression was downregulated in DDP resistant NSCLC tissues and cells. Western blot assay presented a remarkable increase of LC3B‐II/LC3B‐I ratio and a notable decline of p62 level in DDP resistant NSCLC cells, while these effects were weakened by miR‐1. GFP‐LC3 puncta experiment showed that ectopic expression of miR‐1 induced a noticeable downregulation of GFP‐LC3 positive cell percentage in DDP resistant NSCLC cells. Bioinformatical analysis and luciferase assay revealed that autophagy related 3 (ATG3) was a target of miR‐1. Also, Western blot and RT‐qPCR assays manifested that ATG3 was highly expressed in DDP resistant NSCLC tissues and cells. Additionally, miR‐1 inhibited ATG3 expression and ATG3 upregulation abolished miR‐1‐meidated autophagy inhibition in DDP resistant NSCLC cells. Cell Counting Kit‐8 (CCK‐8) assay showed that the half maximal inhibitory concentration (IC50) of cisplatin (DDP) was reduced in miR‐1‐enforced DDP resistant NSCLC cells, but was restored following the overexpression of ATG3. Flow cytometry experiments further showed that miR‐1 overexpression induced a significant upregulation of apoptotic rate and ATG3 restoration weakened miR‐1‐induced apoptosis in DDP resistant NSCLC cells. Collectively, our study validated that miR‐1 overexpression improved DDP sensitivity of NSCLC cells by inhibiting ATG3‐mediated autophagy, providing a potential therapeutic target for easing chemoresistance of anti‐tumor drugs.