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1.
Mol Med Rep ; 14(3): 2213-21, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27430657

ABSTRACT

Despite ongoing research into diabetes and its complications, the underlying molecular associations remain to be elucidated. The systematic identification of molecular interactions in associated diseases may be approached using a network analysis strategy. The biomarker-target interrelated molecules associated with diabetes and its complications were identified via the Comparative Toxicogenomics Database (CTD); the Search Tool for Recurring Instances of Neighboring Genes was utilized for network construction. Functional enrichment analysis was performed with Database for Annotation, Visualization and Integrated Discovery software to investigate connections between diabetes and its complications. A total of 142 (including 122 biomarkers, 10 therapeutic targets and 10 overlapping molecules) biomarker-target interrelated molecules associated with diabetes and its complications were identified via the CTD database, and analysis of the network yielded 1,087 biological processes and fifteen Kyoto Encyclopedia of Genes and Genomes pathways with significant P­values. Various critical aspects of the networks were examined in the present study: a) Intermolecular horizontal and vertical combinations in biomarkers and therapeutic targets associated with diabetes and its complicationb) network topology properties associated with molecular pathological responsec) contribution of key molecules to integrated regulation; and d) crosstalk between multiple pathways. Based on a multi-dimensional analysis, it was concluded that the integrated molecular pathological development of diabetes and its complications does not proceed randomly, which suggests a requirement for integrated, multi-target intervention.


Subject(s)
Biomarkers , Diabetes Complications/etiology , Diabetes Complications/metabolism , Diabetes Mellitus/etiology , Diabetes Mellitus/metabolism , Models, Biological , Neural Networks, Computer , Gene Regulatory Networks , Humans , Metabolic Networks and Pathways , Signal Transduction
2.
Mol Med Rep ; 12(2): 3107-14, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25955305

ABSTRACT

Epithelial ovarian cancer (EOC) remains a major gynecological problem, with a poor 5-year-survival rate due to distant metastases. The identification of microRNAs (miRNAs) may provide a novel avenue for diagnostic and treatment regimens for EOC. Several miRNAs have been reported to be involved in the progression of EOC, among which miRNA (miR)-137 has been observed to be downregulated in the ovarian tissues of patients with EOC. However, the functions of miR-137 in EOC cell apoptosis, migration and invasion remain to be elucidated. In the present study, the expression of miR-137 was measured in clinical ovarian cancer specimens and cell lines using reverse transcription-quantitative polymerase chain reaction. The role of miR-137 in the growth and survival of the SKOV3 human ovarian cancer cell line was determined using several in vitro approaches and in nude mouse models. The results demonstrated that the expression of miR-137 was downregulated in the ovarian cancer specimens and cell lines. It was also observed that enforced expression of miR-137 in the EOC cell lines decreased cell proliferation, clonogenicity, migration and invasion, and induced G1 arrest and cell apoptosis in vitro. Notably, the enforced expression of miR-137 suppressed tumor growth in the nude mice models. These findings suggested that miR-137 may act as a tumor suppressor and be used as a potential therapeutic agent for the treatment of EOC.


Subject(s)
Apoptosis/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Neoplasms, Glandular and Epithelial/genetics , Ovarian Neoplasms/genetics , Animals , Carcinoma, Ovarian Epithelial , Cell Line, Tumor , Cell Movement , Cell Proliferation , Female , G1 Phase Cell Cycle Checkpoints , Humans , Lymph Nodes/metabolism , Lymph Nodes/pathology , Male , Mice , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/metabolism , Middle Aged , Neoplasm Transplantation , Neoplasms, Glandular and Epithelial/metabolism , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Signal Transduction
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