Inhibition of miR-155-5p in non-small cell lung cancer, a potential target for induction of autophagy

Abstract

ObjectivesThe function of autophagy appears to be diverse in cancer. Autophagy also has a complex relationship with apoptosis under different cell conditions. Considering the high mortality and morbidity of Non-small Cell Lung Cancer (NSCLC) around the world, and the potential role of miR-155-5p in cancer progression, we aimed to investigate the autophagy and apoptosis of NSCLC cell line after inhibition of miR-155-5p. Methods and resultsThe antimiR-155-5p and Scramble oligonucleotides were transfected into the A549 human adenocarcinoma lung cancer. After 24 h, the expression level of SIRT1, SIRT2, TP53INP1, and mTOR were evaluated for both groups performing qRT-PCR. After 48 h, the apoptosis assay was also performed using Annexin V-FITC/PI-based flow cytometry. The transfection of antimiR-155-5p decreased the miR-155-5p expression significantly, which increased the expression levels of SIRT1and TP53INP1 as miR-155-5p target genes and expression of SIRT2 as an indirect target. The high expression of SIRT1 inhibited the mTOR pathway leading to enhanced induction of autophagy. The excess autophagy increased the apoptosis rate compared to the scramble group. ConclusionThe exact control of autophagy is an important issue for normal and cancer cells. Here, inhibition of miR-155-5p induced autophagy in a substantial way leading to autophagic cell death. Therefore, targeting miR-155-mediated autophagy might be a potential therapeutic method for NSCLC.