Tumor suppressor microRNA-31 inhibits gastric carcinogenesis by targeting Smad4 and SGPP2.

08:00 EDT 23rd October 2015 | BioPortfolio

Summary of "Tumor suppressor microRNA-31 inhibits gastric carcinogenesis by targeting Smad4 and SGPP2."

To investigate the function of microRNA-31 (miR-31) in the pathogenesis of gastric cancer (GC) and to explore the possible mechanisms involved in it. A quantitative real-time reverse transcription-PCR (RT-PCR) analysis was performed to evaluate miR-31 expression in GC cell lines. After transfecting GC cells with miR-31 precursors, Alamar blue and apoptosis assays were used to measure the respective proliferation and apoptosis rates. SGPP2 and Smad4 expression were determined by real-time RT-PCR and western blot assays after miR-31 transfection. Animal assay was used to further investigate miR-31 in the pathogenesis of GC. miR-31 was significantly reduced in GC tissues and GC cell lines, and that the reduced miR-31 was associated with distant metastasis and GC clinical pathological stages, miR-31 was lower at stages III/IV than that at stage II. SGPP2 and Smad4 were proven to be the direct target of miR-31. SGPP2 and Smad4 at mRNA and protein levels were negatively correlated with miR-31 in human GC tissues and cancer cell lines. Increased miR-31 significantly repressed SGPP2 and Smad4 at transcriptional and translational levels. Functional studies showed that increasing miR-31 inhibited GC cell proliferation, promoted apoptosis and attenuated cell migration, which were also linked to downregulation of STAT3. In vivo, miR-31 inhibited GC cell growth in tumor-bearing mice. This study has revealed miR-31 as a tumor suppressor and has identified SGPP2 and Smad4 as novel targets of miR-31, linking to STAT3 for regulating cancer cell proliferation, apoptosis and migration in GC. Therefore, miR-31 could be a useful biomarker for monitoring GC development and progression, and also could have a therapeutic potential by targeting SGPP2, Smad4 and STAT3 for GC therapy.Cancer Gene Therapy advance online publication, 23 October 2015; doi:10.1038/cgt.2015.41.


Journal Details

This article was published in the following journal.

Name: Cancer gene therapy
ISSN: 1476-5500


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Medical and Biotech [MESH] Definitions

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An E3 UBIQUITIN LIGASE that interacts with and inhibits TUMOR SUPPRESSOR PROTEIN P53. Its ability to ubiquitinate p53 is regulated by TUMOR SUPPRESSOR PROTEIN P14ARF.

A signal transducing adaptor protein and tumor suppressor protein. It forms a complex with activated RECEPTOR-REGULATED SMAD PROTEINS. The complex then translocates to the CELL NUCLEUS and regulates GENETIC TRANSCRIPTION of target GENES.

A product of the p16 tumor suppressor gene (GENES, P16). It is also called INK4 or INK4A because it is the prototype member of the INK4 CYCLIN-DEPENDENT KINASE INHIBITORS. This protein is produced from the alpha mRNA transcript of the p16 gene. The other gene product, produced from the alternatively spliced beta transcript, is TUMOR SUPPRESSOR PROTEIN P14ARF. Both p16 gene products have tumor suppressor functions.

Genes that inhibit expression of the tumorigenic phenotype. They are normally involved in holding cellular growth in check. When tumor suppressor genes are inactivated or lost, a barrier to normal proliferation is removed and unregulated growth is possible.

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