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MicroRNA-26b inhibits tumor metastasis by targeting the KPNA2/c-jun pathway in human gastric cancer
MicroRNAs (miRNA) play an important role in carcinogenesis. Previously, we identified miR-26b as a significantly downregulated miRNA in gastric cancer (GC) tissues (n = 106) based on differential quantitative RT-PCR (RT-qPCR) miRNA expression profiles. In the current study, we aimed to clarify the p...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129949/ https://www.ncbi.nlm.nih.gov/pubmed/27078844 http://dx.doi.org/10.18632/oncotarget.8629 |
Sumario: | MicroRNAs (miRNA) play an important role in carcinogenesis. Previously, we identified miR-26b as a significantly downregulated miRNA in gastric cancer (GC) tissues (n = 106) based on differential quantitative RT-PCR (RT-qPCR) miRNA expression profiles. In the current study, we aimed to clarify the potential role of miR-26b and related target genes in GC progression. Downregulation of miR-26b was associated with advanced tumor-node-metastasis stage (TNM stage) and poor 5-year survival rate. Forced expression of miR-26b led to inhibition of GC cell migration and invasion in vitro and lung metastasis formation in vivo. Conversely, depletion of miR-26b had stimulatory effects. Additionally, miR-26b affected GC cell behavior through negative regulation of the metastasis promoter, karyopherin alpha 2 (KPNA2). Ectopic expression of miR-26b induced a reduction in KPNA2 protein levels, confirmed by luciferase assay data showing that miR-26b directly binds to the 3′ untranslated regions (UTR) of KPNA2 mRNA. Furthermore, miR-26b and KPNA2 mRNA/protein expression patterns were inversely correlated in GC tissues. Cag A of Helicobacter pylori (Hp) enhanced miR-26b levels through regulation of the KPNA2/c-jun pathway. Taken together, our data indicate that miR-26b plays an anti-metastatic role and is downregulated in GC tissues via the KPNA2/c-jun pathway. Based on the study findings, we propose that miR-26b overexpression or KPNA2/c-jun suppression may have therapeutic potential in inhibiting GC metastasis. |
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