Regulation of BGC-823 cell sensitivity to adriamycin via miRNA-135a-5p

Abstract

MicroRNAs (miRNAs) play an important role in the genesis and development of gastric cancer. In the present study, we determined whether miRNA-135a-5p expression was increased in gastric cancer compared with adjacent non-tumor tissues using 20 pairs of gastric cancer and para-carcinoma tissue samples which were assessed via microarray and bioinformatics analysis, and western blotting. The protein content detection showed that miRNA-135a-5p expression was inversely correlated with AP-2α. Bioinformatics analysis revealed that AP-2α contains a putative miRNA-135a-5p target, which was confirmed as a direct target using the 3′-UTR luciferase reporter system. Additionally, an increase and decrease of miRNA-135a-5p inhibited or impaired adriamycin-induced apoptosis in BGC-823 cells (p<0.05, compared with the group without gene intervention), respectively. Luciferase reporter experiments confirmed that AP-2α bound to the BCL-2 promoter and affected its transcription. Therefore, miRNA-135a-5p increased BCL-2 via AP-2α and consequently enhanced cell resistance to apoptosis. This newly identified miRNA-135a-5p-AP-2α-BCL-2 pathway provides insight for the treatment of gastric cancer and solution for insensitivity of gastric cancer to chemotherapy drugs.