Mechanism of miR-210 involved in epithelial–mesenchymal transition of pancreatic cancer cells under hypoxia

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Abstract

Purpose: To investigate the possible mechanism of miR-210 involved in epithelial-mesenchymal transition (EMT) of pancreatic cancer cells under hypoxia. Methods: In this study, we used the following approaches. Hypoxic microenvironment was stimulated in vitro, and the CCK-8 assay was used to analyze cell viability. The MiRNA expression level was measured by qRT-PCR. HOXA9, EMT-related proteins, and NF-κB activities were examined by immunoblotting assay. Dual luciferase reporter assay was used to assess whether HOXA9 was a target of miR-210.Results: Under hypoxia condition, miR-210, HIF-1α and NF-κB were increased, and the HOXA9 was reduced in PANC-1 cells. When miR-210 was overexpressed in normoxic PANC-1 cells, EMT epithelial markers of E-cadherin and β-catenin were down-regulated, and mesenchymal markers of vimentin and N-cadherin were up-regulated to promote cell migration/invasive ability, and the HOXA9 level was decreased. After HOXA9 level decreased, the sensitivity to chemotherapeutic drug of gemcitabine was reduced, NF-κB expression level and cell migration/invasive ability was enhanced. Whereas, miR-210 antagonist into hypoxic PANC-1 cells, which up-regulated E-cadherin, β-catenin level, and down-regulated vimentin and N-cadherin levels to decrease cell migration/invasive ability, and increase the HOXA9. Furthermore, increasing HOXA9 level decreased NF-κB expression level and cell migration/invasive ability, enhanced the sensitivity to gemcitabine. At last, miRDB and TargetScan predicted that HOXA9 was a target of miR-210, and dual luciferase reporter assay verified this hypothesis.Conclusion: MiR-210 inhibited the expression of HOXA9 to activate the NF-κB signaling pathway and mediated the occurrence of EMT of pancreatic cancer cells induced by HIF-1α under hypoxia.

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