Human antigen R affects the migration and invasion of human lung cancer A549 cells and regulates E-cadherin suppressor Snail

Recent studies demonstrated that the progression and metastasis of lung cancer were associated with human antigen R (HuR), a post-transcriptional RNA-binding protein that stabilizes and regulates the expression of many tumor-related genes. Although HuR was shown to affect the expressions of epithelial cadherin (E-cadherin), a tumor migration suppressor, in airway epithelial cells, esophageal squamous and colon cancer cells, direct evaluation of the effect and mechanism of HuR on the migration and invasion of lung cancer cells is not documented. In this study, HuR was knocked down via RNA interference and overexpressed using recombinant plasmid in adenocarcinomic human alveolar basal epithelial A549 cells. No apparent inhibition of cell viability was observed. HuR knockdown significantly suppressed A549 migration and invasion in scratch wound healing and transwell assays, with an increase in E-cadherin expression and a decrease in N-cadherin expression, while the overexpression of HuR notably facilitated A549 migration and invasion, with a decrease in E-cadherin level and an increase in N-cadherin level. In addition, immunoprecipitation study showed that HuR directly interacted with Snail, a repressor of E-cadherin, and upregulated the expression of Snail in A549 cells. These combined results suggested that the effect of HuR on A549 migration and invasion might be realized by stabilizing and increasing the expression of Snail, which in-turn interfered with the expressions of E-cadherin and N-cadherin. The finding of this study revealed direct evidence that HuR affected the migration and invasion of lung cancer cells and regulated E-cadherin, N-cadherin and Snail expressions, providing an additional reference and mechanistic clue for further researches and therapeutic strategies in treating lung cancer. Copyright: (c) 2022 by the C.M.B. Association. All rights reserved.