Abstract
Introduction Breast cancer (BC) is a common malignant tumor affecting women across the world. LncRNAs are frequently implicated in the course of BC. The current study set out to determine the specific effect of lncRNA AGAP2-AS1 on BC cell resistance to apoptosis. Methods AGAP2-AS1 expression patterns in BC tissues and cells were evaluated. si-AGAP2-AS1 was transfected into MCF-7 cells, followed by the assessment of cell proliferation and apoptosis. In addition to detection of MTA1 expression patterns, the binding relation between AGAP2-AS1 and HuR was verified using RNA pull-down and RNA immunoprecipitation. Next, the regulation enrichment of AGAP2-AS1- and HuR to H3K27ac recruitment in the MTA1 promoter was analyzed. MCF-7 cell resistance to apoptosis was observed after the combined experiment of histone deacetylase inhibitor M344 and si-AGAP2-AS1. Lastly, xenografts tumors were established to detect tumor weight and volume, tumor apoptosis and growth as well as expression of AGAP2-AS1 and MTA1. Results AGAP2-AS1 was overexpressed in BC tissues and cells, and AGAP2-AS1 silencing inhibited cell proliferation but facilitated apoptosis. Physiologically, AGAP2-AS1 bound to HuR to stabilize its own expression, and AGAP2-AS1-HuR complex upregulated H3K27ac levels in the MTA1 promoter region to elevate MTA1 promoter activity and MTA1 expression. H3K27ac upregulation partially-annulled the promotive effect of si-AGAP2-AS1 on BC apoptosis by upregulating MTA1. si-AGAP2-AS1 in vivo inhibited MTA1 expression to enhance apoptosis and suppress tumor growth. Conclusion Collectively, our findings indicated that AGAP2-AS1 bound to HuR to stabilize its own expression, and AGAP2-AS1-HuR complex enhanced H3K27ac levels in the MTA1 promoter region to improve MTA1 promoter activity and MTA1 expression in BC cells, so as to augment BC cell resistance to apoptosis.