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MicroRNA-145 exerts tumor-suppressive and chemo-resistance lowering effects by targeting CD44 in gastric cancer
AIM: To determine the potential roles of CD4 and microRNA (miR)-145 in gastric cancer. METHODS: The levels of CD44 and miR-145 were determined in gastric cancer cells. Quantitative real-time polymerase chain reaction was used to measure to the level of CD44 mRNA. A luciferase reporter assay and west...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Baishideng Publishing Group Inc
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385400/ https://www.ncbi.nlm.nih.gov/pubmed/28428713 http://dx.doi.org/10.3748/wjg.v23.i13.2337 |
Sumario: | AIM: To determine the potential roles of CD4 and microRNA (miR)-145 in gastric cancer. METHODS: The levels of CD44 and miR-145 were determined in gastric cancer cells. Quantitative real-time polymerase chain reaction was used to measure to the level of CD44 mRNA. A luciferase reporter assay and western blotting were performed to examine the effect of miR-145 on CD44 expression. Tumor sphere and MTT assays were carried out to evaluate the self-renewal and chemo-resistance properties of gastric cancer cells. RESULTS: The expression of CD44 was greatly increased and miR-145 was decreased in gastric cancer cells that were highly enriched in cancer stem cells (CSCs). The results demonstrated that miR-145 regulated CD44 by targeting directly the CD44 3’-untranslated region (3’-UTR). In gastric cancer cells, overexpression of miR-145 repressed the activity of the CD44 3’-UTR, and disruption of miR-145/CD44 3’-UTR interactions abrogated the silencing effects. In addition, miR-145 inhibition stimulated CD44 3’-UTR activity and disruption of miR-145/CD44 3’-UTR interactions abrogated this stimulatory effect. Enforced CD44 expression greatly increased tumor sphere formation and chemo-resistance in gastric cancer cells. Furthermore, the inhibition of CSCs and the chemo-sensitivity of gastric cancer cells treated with miR-145 were significantly abrogated by overexpression of CD44. CONCLUSION: miR-145 targeting of CD44 plays critical roles in the regulation of tumor growth and chemo-resistance in gastric cancer. |
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