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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, RESULTS. Meshes: Adenocarcinoma, Aged, Biomarkers, Tumor, Cell Proliferation, Female, Gastric Mucosa, Gene Expression Regulation, Neoplastic, Humans, Immunoenzyme Techniques, In Situ Hybridization, Male, MicroRNAs, Molecular Chaperones, Neoplasm Staging, Prognosis, Protein Inhibitors of Activated STAT, RNA, Messenger, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, STAT3 Transcription Factor, Stomach, Stomach Neoplasms, Tissue Array Analysis, Tumor Cells, Cultured.
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Does microRNA-18a modulate STAT3 activity through negative regulation of PIAS3 during gastric adenocarcinogenesis? Context: MicroRNA (miRNA, miR)-18a is a member of the miR-17-92 cluster, an important locus that is markedly overexpressed in several cancers and associated with cancer development and progression. However, the mechanism of action of the miR-17-92 cluster and its individual miRNAs are largely unknown. In this study, we investigated the expression of the miR-17-92 cluster by in situ hybridisation (ISH) assay and copy-number analysis in gastric tissue microarray (TMA) specimens. We determined that miR-18a was present at higher levels than the other five miRNAs in the cluster. In addition, we identified Protein Inhibitor of Activated Signal Transducer and Activator of Transcription 3 (PIAS3) as a direct target of miR-18a in gastric cancer. miR-18a level was positively correlated with levels of Survivin, Bcl-xL, and c-Myc, which are downstream transcriptional targets of Signal Transducer and Activator of Transcription 3 (STAT3). STAT3-induced transcription can be negatively regulated by PIAS3; consistent with this, PIAS3 level was negatively correlated with levels of Survivin, Bcl-xL, and c-Myc.
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Our findings indicate that miR-18a acts as an oncogene and plays a role in gastric adenocarcinogenesis, at least in part by negatively regulating PIAS3 and thereby modulating expression of STAT3 target genes. Final Decision: yes