Hypoxia promotes pancreatic cancer progression by triggering cancer cell invasion. However, the mechanism underlying this process remains unclear, hindering the development of effective therapies. The present study aimed to delineate the molecular mechanisms underlying the prometastatic effect of hypoxia in pancreatic cancer cells. The expression of microRNA-150 (miRNA-150) was detected using reverse transcription-quantitative polymerase chain reaction in pancreatic cancer samples and in the hypoxia-induced CaPan2 human pancreatic cancer cell line. The target gene was identified using bioinformatics and a luciferase reporter assay. Inhibition of the expression of C-X-C chemokine receptor type 4 (CXCR4) by miRNA-150 was confirmed using transfection with miRNA-150 mimics. The prometastatic effect of hypoxia was detected using migration assays. The expression of miRNA-150 was shown to be downregulated in pancreatic cancer samples compared with that in normal pancreatic tissue samples. Furthermore, its expression was reduced in hypoxia-induced CaPan2 cells, compared with that in control cells. Bioinformatics and the results of the luciferase reporter assay, demonstrated that miRNA-150 inhibited the expression of CXCR4 by directly targeting the 3' untranslated region of CXCR4 mRNA. The results of the migration assay showed that hypoxia promotes cell migration and invasion. However, this prometastatic effect was reversed by transfection with miRNA-150 mimics. The present results suggest that hypoxia promotes pancreatic cancer migration by downregulating miRNA-150.
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http://dx.doi.org/10.3892/ol.2015.3344 | DOI Listing |
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Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47907, United States.
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D'Or Institute for Research and Education, Digestive Surgery Residency Program - Rio de Janeiro (RJ), Brazil.
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Universidade de São Paulo, Faculty of Medicine - São Paulo (SP), Brazil.
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Instituto D'Or de Pesquisa e Ensino, Digestive Surgery Program - Rio de Janeiro (RJ), Brazil.
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