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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: OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Apoptosis Regulatory Proteins, Carcinoma, Pancreatic Ductal, Cell Line, Tumor, Cell Proliferation, Disease Progression, Endosomal Sorting Complexes Required for Transport, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, Humans, Immediate-Early Proteins, Mice, MicroRNAs, Nedd4 Ubiquitin Protein Ligases, Pancreatic Neoplasms, Prognosis, RNA, Messenger, RNA-Binding Proteins, Tumor Suppressor Proteins, Ubiquitin-Protein Ligases.
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Do microRNAs cooperatively inhibit a network of tumor suppressor genes to promote pancreatic tumor growth and progression? Context: There has not been a broad analysis of the combined effects of altered activities of microRNAs (miRNAs) in pancreatic ductal adenocarcinoma (PDAC) cells, and it is unclear how these might affect tumor progression or patient outcomes. We combined data from miRNA and messenger RNA (mRNA) expression profiles and bioinformatic analyses to identify an miRNA-mRNA regulatory network in PDAC cell lines (PANC-1 and MIA PaCa-2) and in PDAC samples from patients. We used this information to identify miRNAs that contribute most to tumorigenesis. We identified 3 miRNAs (MIR21, MIR23A, and MIR27A) that acted as cooperative repressors of a network of tumor suppressor genes that included PDCD4, BTG2, and NEDD4L. Inhibition of MIR21, MIR23A, and MIR27A had synergistic effects in reducing proliferation of PDAC cells in culture and growth of xenograft tumors in mice. The level of inhibition was greater than that of inhibition of MIR21 alone. In 91 PDAC samples from patients, high levels of a combination of MIR21, MIR23A, and MIR27A were associated with shorter survival times after surgical resection.
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In an integrated data analysis, we identified functional miRNA-mRNA interactions that contribute to growth of PDACs. These findings indicate that miRNAs act together to promote tumor progression; therapeutic strategies might require inhibition of several miRNAs. Final Decision: yes