LncRNA HOXD-AS1 affects proliferation and apoptosis of cervical cancer cells by promoting FRRS1 expression via transcription factor ELF1
Huan Liu, Li Liu, Qiong Liu, Fengjiao He, Hong Zhu
Abstract
To investigate the function of lncRNA HOXD-AS1 in cervical squamous cell carcinoma (CESC) and the underlying mechanism. The expressions of HOXD-AS1 and FRRS1 were analyzed on the online software GEPIA based on CESC-related information in The Cancer Genome Atlas (TCGA). Cervical cancer cells (SiHa and Hela) were accordingly transfected with pCDNA3.1-HOXD-AS1, sh-HOXD-AS1, sh-FRRS1 or pCDNA3.1-ELF1. After cell transfection, CCK-8, EDU and flow cytometry were applied for measurement of cell vitality, quantity and apoptosis, respectively. The relationship between HOXD-AS1 and FRRS1 was predicted on the online software LncMap and further verified by RNA binding protein immunoprecipitation. Nude mice were injected with stabilized SiHa cells transfected with sh-HOXD-AS1 to assess the tumorigenic ability of HOXD-AS1 in vivo. Immunohistochemistry detected the expression of the proliferation marker Ki-67. The levels of HOXD-AS1, ELF1 and FRRS1 were measured in vivo and in vitro. HOXD-AS1 and FRRS1 were overexpressed in CESC. After transfection of sh-HOXD-AS1, sh-ELF1 or sh-FRRS1, the proliferation of SiHa and Hela cells was inhibited and their apoptosis was promoted; while HOXD-AS1 overexpression had opposite effects on CESC development. Co-transfection of sh-FRRS1 and pCDNA3.1-HOXD-AS1 could abolish the tumor suppressive effect of FRRS1 knockdown. HOXD-AS1 elevated the level of FRRS1 by binding ELF1. Furthermore, HOXD-AS1 contributed to the CESC growth in mouse models. HOXD-AS1 promotes CESC by up-regulating FRRS1 via ELF1.