LncRNA HOXD-AS1 affects proliferation and apoptosis of cervical cancer cells by promoting FRRS1 expression via transcription factor ELF1

Abstract

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.