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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, METHODS, RESULTS. Meshes: Aged, Animals, Carcinoma, Pancreatic Ductal, Cell Movement, Cell Proliferation, Disease Progression, Female, Gene Expression Regulation, Neoplastic, HEK293 Cells, Humans, Immunohistochemistry, In Situ Hybridization, Lymphatic Metastasis, Male, Mice, Mice, Nude, MicroRNAs, Middle Aged, Multivariate Analysis, Neoplasm Invasiveness, Neoplasm Transplantation, Pancreatic Neoplasms, Pancreaticoduodenectomy, Prognosis, Real-Time Polymerase Chain Reaction, Smad4 Protein, Tissue Array Analysis.
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Does microRNA-301a-3p promote pancreatic cancer progression via negative regulation of SMAD4? Context: Aim to determine the clinicopathological and prognostic role of miR-301a-3p in pancreatic ductal adenocarcinoma(PDAC), to investigate the biological mechanism of miR-301a-3p in vitro and in vivo. By tissue microarray analysis, we studied miR-301a-3p expression in PDAC patients and its clinicopathological correlations as well as prognostic significance. qRT-PCR was used to test miR-301a-3p expression in PDAC tissues and cell lines. Functional experiments including in vitro and in vivo were performed. Significantly higher expression of miR-301a-3p were found in PDAC patients with lymph node metastasis and advanced pathological stages and identified as an independent prognostic factor for worse survival. In PDAC samples and cell lines, miR-301a-3p was significantly up-regulated compared with matched non-tumor tissues and normal pancreatic ductal cells, respectively. Overexpression of miR-301a-3p enhanced PDAC cells colony, invasion and migration abilities in vitro as well as tumorigenicity in vivo. Furthermore, SMAD4 was identified as a target gene of miR-301a-3p by cell as well as mice xenograft experiments. In PDAC tissue microarray, a significantly inverse correlation between miR-301a-3p ISH scores and SMAD4 IHC scores were observed in both tumor and corresponding non-tumor tissues.
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MiR-301a-3p functions as a novel oncogene in PDAC and the oncogenic activity may involve its inhibition of the target gene SMAD4. Final Decision: yes