期刊
ONCOLOGY REPORTS
卷 32, 期 6, 页码 2549-2556出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2014.3546
关键词
gastric cancer; AP-2 alpha; anti-apoptosis; miRNA135a-5p; BCL-2
类别
资金
- National Science Foundation of China [81372293, 81241088, 81273161]
- New Century Excellent Talents in Heilongjiang Province University
- Post-Doctoral Science Foundation of China [2012M520762]
- Department of Education of Heilongjiang Province of China [12531736]
- Program for Innovation Research Team in Science and Technology in Heilongjiang Province University
- China Scholarship Council
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-2 alpha. Bioinformatics analysis revealed that AP-2a 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-2 alpha bound to the BCL-2 promoter and affected its transcription. Therefore, miRNA-135a-5p increased BCL-2 via AP-2 alpha and consequently enhanced cell resistance to apoptosis. This newly identified miRNA-135a-5p-AP-2 alpha-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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