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

Pan,Yanming; Ren,Fengyun; Zhang,Wei; Liu,Guibo; Yang,Dan; Hu,Jing; Feng,Kejian; Feng,Yukuan

doi:10.3892/or.2014.3546

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

Authors:
- Yanming Pan
- Fengyun Ren
- Wei Zhang
- Guibo Liu
- Dan Yang
- Jing Hu
- Kejian Feng
- Yukuan Feng
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Affiliations: Key Laboratory of Tumor Prevention and Treatment (Heilongjiang Higher Education Institutions), Mudanjiang Medical University, Mudanjiang 157011, P.R. China, Department of Respiration, Hongqi Hospital of Mudanjiang Medical University, Mudanjiang 157011, P.R. China, School of Basic Medical Science, Mudanjiang Medical University, Mudanjiang 157011, P.R. China
Published online on: October 14, 2014 https://doi.org/10.3892/or.2014.3546
Pages: 2549-2556

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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.

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