MicroRNA-125a attenuates the chemoresistance against ubenimex in non-small cell lung carcinoma via targeting the aminopeptidase N signaling pathway.

Abstract

Since several long noncoding RNAs (lncRNAs) have been implicated in the development of chemoresistance in non-small cell lung carcinoma (NSCLC), the aim of this study was to investigate whether antisense noncoding RNA in the INK4 locus (ANRIL) was associated with the chemoresistance of NSCLC. Real-time polymerase chain reaction was performed to identify potential lncRNAs involved in the chemoresistance of NSCLC, while in-silicon analyses and luciferase assays were carried out to explore the regulatory relationship among ANRIL, miR-125a, and aminopeptidase N (APN). Ubenimex resistant cells were associated with a high expression of ANRIL, which directly binds to miR-125a. MiR-125a directly targeted APN expression. In addition, miR-125a and ANRIL small interfering RNA inhibited the expression of APN but promoted the expression of beclin-1 and LC3, whereas ANRIL, by competing with miR-125a, promoted cell proliferation and inhibited cell apoptosis. The data of this study suggested that, by targeting ANRIL and the APN signaling pathway, miR-125a inhibited the proliferation of NSCLC cells and promoted their apoptosis, thus attenuating the chemoresistance of NSCLC against Ubenimex.