Downregulation of microRNA-128-3p protects human esophageal squamous Het-1A cells from hydrochloric acid-induced cell injury by targeting E2F3.

PHARMAZIE(2018)

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摘要
This study aimed to investigate the role of microRNA-128-3p in regulating hydrochloric acid (HCl)-induced cell injury in human esophageal squamous Het-1A cells. Het-1A cells were treated with HCl (pH 4.0) to induce esophageal injury like this caused by reflux. Whether HCl induced cell injury was then assessed by detecting cell proliferation and apoptosis. The expression of miR-128-3p in HCl-treated Het-1A cells was investigated, followed by investigating the effects of miR-128-3p overexpression and suppression on HCl-induced Het-1A cell injury. In addition, the target of miR-128-3p was identified. Besides, the association between miR-128-3p and ERK and PI3K/AKT pathways was further explored. HCl inhibited the proliferation and increased apoptosis of Het-1A cells. miR-128-3p was upregulated in Het-1A cells after HCl treatment. Inhibition of miR-128-3p alleviated HCl-induced Het-1A cell injury, whereas miR-128-3p overexpression further aggravated this injury. Moreover, E2F3 was confirmed as a target of miR-128-3p, which could be negatively regulated by miR-128-3p. Besides, miR-128-3p inhibition remarkably alleviated the inhibitory effects of HCl on the activation of ERK and PI3K/AKT pathways, which were further reversed after inhibition of miR-128-3p and E2F3 at the same time. Alltogether, our findings indicate that downregulation of microRNA-128-3p may protect human esophageal squamous cells Het-1A from HCl-induced cell injury via targeting E2F3 and inhibiting the activation of ERK and PI3K/AKT pathways. These findings provide the experimental basis for targeted treatment of reflux esophagitis.
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