siRNA directed against Annexin II receptor inhibits HeLa cell proliferation, migration and invasion and induces apoptosis via suppressing ERK1/2 and Akt signaling pathways.

Annexin II receptor (AXIIR) was originally identified as a cell surface receptor for Annexin II and was shown to be involved in the development and progression of multiple cancers, but little was known about its role in cervical cancer. The aim of our study was to investigate the role and the plausible molecular mechanism of AXIIR in regulating apoptosis, invasion and migration of cervical cancer cells. siRNA targeting AXIIR was chemical synthesized and transfected into HeLa cells which with non-specific siRNA tranfection used as a negative control. Cell proliferation, cell migration, cell invasion and cell apoptosis assay were measured by CCK-8, wound healing assay, Transwell invasion assay and flow cytometry, respectively. Tumor-related protein and signaling pathway were also measured by real-time quantitative PCR and western blot assay to investigate the molecular mechanism of AXIIR involved in regulating HeLa cells. Our data showed that AXIIR siRNA significantly inhibited HeLa cell viability and induced cell apoptosis by increases in Caspase-3/-8/-9 mRNA and protein expression, and inhibit HeLa cell migration and invasion by decreased MMP-2/-9 mRNA and protein expression. AXIIR siRNA could also significantly down-regulate Akt, p-Akt, ERK1/2 and p-ERK1/2 expression. In conclusion, AXIIR is of great importance for regulatingcell viability, migration, invasion and apoptosis . The molecular mechanism of AXIIR might be the activation of PI3K/Akt and ERK1/2 signaling pathway, indicating a critical regulator function of AXIIR in tumorigenic responses of cervical cancer.