AKR1C2 small interfering RNA (siRNA) inhibited beta-catenin expression and transcriptional activation in human liver cancer cell line QGY7701.
OBJECTIVE
It has been proved that changes in the Wnt/beta-catenin pathway lead to hepatocarcinogenesis and the AKR1C2 gene may contribute to the occurrence, advancement and invasiveness of liver cancer. The purpose of this study is to investigate AKR1C2 small interfering RNA (siRNA) influence on beta-catenin expression and transcriptional activation in the human liver cancer cell line QGY7701.


METHODS
We constructed AKR1C2 small interfering RNA (siRNA) expression vector pSilence2.1/ U6/AKR1C2 RNAi and then transfected it into the liver cancer cell QGY7701. Beta-catenin mRNA and its protein expression was detected by RT-PCR, western blotting and beta-catenin gene transcriptional activity was analyzed by luciferase assay.


RESULTS
AKR1C2 siRNA inhibited the transcriptional expression of beta-catenin and decreased beta-catenin protein stability in QGY7701. AKR1C2 siRNA inhibited beta-catenin gene transcriptional regulation and control activity for TCF gene by influencing on the down-stream gene's function of beta-catenin in QGY7701 liver cancer cells.


CONCLUSIONS
It suggests a causative cooperative role for beta-catenin and AKR1C2 in tumorigenesis. Thus, the inhibition of activation of the beta-catenin/ TCF-signaling pathway is believed to be one mechanism by which AKR1C2 siRNA exerts a gatekeeper function during hepatocarcinogenesis.
Lu
Dong-Dong
DD
Tongji University School of Life Science and Technology, Shanghai, 200092, People's Republic of China. ludondon88@163.com
D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D051822:T Cell Transcription Factor 1 / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)
D006913:Hydroxysteroid Dehydrogenases; D034741:RNA, Small Interfering; D051822:T Cell Transcription Factor 1; D051176:beta Catenin; C497576:TCF7 protein, human; C435496:AKR1C2 protein, human; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)