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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Regulation of BGC-823 cell sensitivity to adriamycin via miRNA-135a-5p
Yanming Pan1, Fengyun Ren1, Wei Zhang2
1Key Laboratory of Tumor Prevention and Treatment (Heilongjiang Higher Education Institutions), Mudanjiang Medical University, Mudanjiang 157011, P.R. China.
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 inhi-bited 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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