LncRNA RHPN1-AS1 promoted cell proliferation, invasion and migration in cervical cancer via the modulation of miR-299-3p/FGF2 axis

Aims: This study aims to determine the biological function and underlying mechanisms of lncRNA RHPN1 antisense RNA1 (RHPN1-AS1) in cervical cancer cell proliferation, invasion and migration.

Main methods: Gene expression was analysed by quantitative real-time PCR; protein levels were determined by western blot assay; in vitro functional assays determined the cervical cancer cell progression; in vivo tumor growth of cervical cancer cell was determined in nude mice xenograft models.

Key findings: The results showed that RHPN1-AS1 was up-regulated in cervical cancer tissues and cell lines. In vitro functional assays demonstrated that RHPN1-AS1 overexpression promoted SiHa cell proliferation, invasion and migration; while RHPN1-AS1 knockdown showed the opposite effects. In vivo study showed that RHPN1-AS1 knockdown suppressed tumor growth in the nude mice. Further investigation showed that miR-299-3p was targeted and inversely regulated by RHPN1-AS1. In addition, miR-299-3p targeted the 3' untranslated region of fibroblast growth factor 2 (FGF2) to suppress its expression. The rescue experiments showed that the enhanced effects of RHPN1-AS1 overexpression on cell proliferation, growth, invasion and migration in SiHa cells were significantly attenuated by miR-299-3p overexpression or FGF2 inhibition. On the other hand, knockdown of miR-299-3p and overexpression of FGF2 both significantly increased cell proliferation, growth, invasion and migration in SiHa cells transfected with RHPN1-AS1 siRNA.

Significance: In conclusion, our results revealed that RHPN1-AS1 promoted cervical cancer progression via targeting miR-299-3p/FGF2 axis. Our data suggested that RHPN1-AS1/miR-299-3p/FGF2 axis may be a promising target for cervical cancer treatment.