HPV18 E7 induces the over-transcription of eIF4E gene in cervical cancer.
OBJECTIVE
Eukaryotic translation initiation factor 4E (eIF4E) is overexpressed in cervical cancer (CC). However, the molecular mechanisms are unclear. This study aimed to investigate the molecular mechanism of eIF4E gene overexpression in CC.


METHODS
The human papillomavirus (HPV) type 18 E7 and eIF4E mRNAs were measured following knock down or overexpression of E7 gene by RT-PCR and real-time PCR. Cell counting kit-8 assay was used to determine the cell proliferation. Flow cytometry was used to analyze the cell cycle and apoptosis. Transwell system was employed to determine the cell migration.


RESULTS
Overexpression of E7 gene increased eIF4E mRNA level by 24.3% (P<0.01) in HPV negative C33A cells. Knock down of E7 decreased markedly eIF4E mRNA by 73% (P<0.01) in HPV18 positive HeLa cells. Under the state of high expression of E7, 1) up-regulation of eIF4E drastically promoted the cell proliferation, cell cycle and cell migration, and inhibited the cell apoptosis. 2) down-regulation of eIF4E significantly inhibited the cell proliferation, cell cycle and the ability of cell migration, and also promoted the apoptosis of cervical cancer cells.


CONCLUSIONS
HPV E7 induced eIF4E gene over transcription which might be a new marker for CC. The finding broadens the understanding of the CC carcinogenesis.
Obstetrics and Gynecology Department of the first Affiliated Hospital of Guangdong Medical College, No. 57 Avenue of the people, Zhanjiang, Guangdong Province 524023, PR China ; Cancer Institute of Guangdong Medical College, No. 1 Xincheng Road, Dongguan, Guangdong Province 523808, PR China.
Tianyun
T
Pang
Cancer Institute of Guangdong Medical College, No. 1 Xincheng Road, Dongguan, Guangdong Province 523808, PR China.
Sen
S
Wang
Cancer Institute of Guangdong Medical College, No. 1 Xincheng Road, Dongguan, Guangdong Province 523808, PR China ; People's Hospital of Dongguan, No. 3 South of Wandao Road, Dongguan, Guangdong Province 523059, PR China.
Min
M
Gao
Cancer Institute of Guangdong Medical College, No. 1 Xincheng Road, Dongguan, Guangdong Province 523808, PR China.
Haixian
H
Kang
Cancer Institute of Guangdong Medical College, No. 1 Xincheng Road, Dongguan, Guangdong Province 523808, PR China.
Yi
Y
Zhao
Pathology Department of Guangdong Medical College, No. 1 Xincheng Road, Dongguan, Guangdong Province 523808, PR China.
Yunhong
Y
Yao
Cancer Institute of Guangdong Medical College, No. 1 Xincheng Road, Dongguan, Guangdong Province 523808, PR China ; Pathology Department of Guangdong Medical College, No. 1 Xincheng Road, Dongguan, Guangdong Province 523808, PR China.
Xinrong
X
Hu
Cervical cancer; E7; EIF4E; HPV