Suppression of hLRH-1 mediated by a DNA vector-based RNA interference results in cell cycle arrest and induction of apoptosis in hepatocellular carcinoma cell BEL-7402.
RNA interference (RNAi) is the process by which double-stranded RNA directs sequence-specific degradation of mRNA. A DNA vector-based approach has been shown to be able to trigger RNA interference in mammalian cells successfully. LRH-1 is an orphan nuclear receptor predominantly expressed in tissues of endodermal origin, where it controls development and cholesterol homeostasis. In the present study, we demonstrated that the expression of hLRH-1 and cyclin E1 in BEL-7402 cells could be suppressed by up to approximately 80% via DNA vector-based RNA interference. The suppression of hLRH-1 resulted in cell cycle arrest mediated by the down-regulation of cyclin E1. Induction of apoptosis and down-regulation of Gadd45beta were also shown in hLRH-1 knock down BEL-7402 cells. These results, together with the findings that Gadd45beta remained unchanged in cyclin E1 RNAi cells, suggested that the induction of apoptosis by knock down of hLRH-1 was closely related to the down-regulation of Gadd45beta.
Wang
Shuiliang
S
Center for Laboratory Medicine, Fuzhou General Hospital, Fuzhou, Fujian 350025, PR China.
Lan
Fenghua
F
Huang
Lianghu
L
Dong
Lihong
L
Zhu
Zhongyong
Z
Li
Zonghai
Z
Xie
Youhua
Y
Fu
Jiliang
J
D000943:Antigens, Differentiation / Q000378:metabolism; D017209:Apoptosis; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D005434:Flow Cytometry; D005822:Genetic Vectors; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D034622:RNA Interference; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000037:antagonists & inhibitors*; D000097642:GADD45 Proteins
D000943:Antigens, Differentiation; D004247:DNA; D017931:DNA Primers; D004268:DNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C086470:GADD45B protein, human; D000097642:GADD45 Proteins; C082631:NR5A2 protein, human