LncRNA HIF1A-AS2 modulated by HPV16 E6 regulates apoptosis of cervical cancer cells via P53/caspase9/caspase3 axis

Abstract

BackgroundPlentiful evidence proves that lncRNAs play a crucial role in tumor development. However, the function and mechanism that were mediated by lncRNA HIF1A-AS2 in cervical cancer remain unclear. MethodsThe lncRNA HIF1A-AS2 was identified via high-throughput microarray analysis of three HPV 16-positive cervical squamous cell carcinoma (CSCC) samples and three HPV-negative normal controls. The expression of HIF1A-AS2 was detected by qRT-PCR in clinical tissues and cancer cells. In vitro and in vivo assays were performed through downregulation or upregulation of HIF1A-AS2. The possible mechanisms of HIF1A-AS2 in cervical cancer cells were explored by western blot, flow cytometric analysis and rescue assays. ResultsHIF1A-AS2 was significantly increased in cervical cancer tissue, and in the HPV- positive cervical cancer cells. Further investigation showed that the inhibition of HIF1A-AS2 suppressed cell proliferation, migration, invasion, and induced apoptosis, while up-regulation of HIF1A-AS2 revealed opposite results. In terms of mechanism, we found that HIF1A-AS2 was mediated by HPV16 E6 and regulated cell apoptosis via P53/caspase 9/caspase 3 axis. ConclusionOur findings demonstrate that HIF1A-AS2 functions as a carcinogenic lncRNA that promotes tumor development, and serves as a candidate prognostic factor, which may contribute to the treatment of cervical cancer.