title: 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 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.
authors.affiliation: Key Laboratory of Tumor Prevention and Treatment (Heilongjiang Higher Education Institutions), Mudanjiang Medical University, Mudanjiang 157011, P.R. China.
authors.forename: Yanming
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Key Laboratory of Tumor Prevention and Treatment (Heilongjiang Higher Education Institutions), Mudanjiang Medical University, Mudanjiang 157011, P.R. China.
authors.forename: Fengyun
authors.initials: F
authors.lastname: Ren
authors.affiliation: Department of Respiration, Hongqi Hospital of Mudanjiang Medical University, Mudanjiang 157011, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: School of Basic Medical Science, Mudanjiang Medical University, Mudanjiang 157011, P.R. China.
authors.forename: Guibo
authors.initials: G
authors.lastname: Liu
authors.affiliation: Key Laboratory of Tumor Prevention and Treatment (Heilongjiang Higher Education Institutions), Mudanjiang Medical University, Mudanjiang 157011, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
authors.affiliation: Key Laboratory of Tumor Prevention and Treatment (Heilongjiang Higher Education Institutions), Mudanjiang Medical University, Mudanjiang 157011, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.affiliation: School of Basic Medical Science, Mudanjiang Medical University, Mudanjiang 157011, P.R. China.
authors.forename: Kejian
authors.initials: K
authors.lastname: Feng
authors.affiliation: Key Laboratory of Tumor Prevention and Treatment (Heilongjiang Higher Education Institutions), Mudanjiang Medical University, Mudanjiang 157011, P.R. China.
authors.forename: Yukuan
authors.initials: Y
authors.lastname: Feng
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D011401:Promoter Regions, Genetic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D013274:Stomach Neoplasms / Q000378:metabolism; D050656:Transcription Factor AP-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; C000595707:BCL2 protein, human; C544965:MIRN135 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D050656:Transcription Factor AP-2; D004317:Doxorubicin