The high-risk HPV oncogene E7 upregulates miR-182 expression through the TGF-β/Smad pathway in cervical cancer.
Accumulating experimental evidence has shown that the aberrant expression of microRNAs (miRNAs) is involved in the development and progression of human cervical cancer. Previously, we identified miR-182 as an oncomiRNA in cervical cancer. However, the mechanism by which miR-182 is regulated and the interaction between human papillomavirus (HPV) and miR-182 in cervical cancer development remains unknown. In the present study, we explored the link between HPV E7 and miR-182 and verified that high-risk HPV E7 upregulated miR-182 expression through TGF-β/Smad4 signaling pathway in cervical cancer. By contrast, low-risk HPV E7 did not affect the expression of TGF-β and miR-182. Mechanistically, as high-risk HPV E7 bound to pRb, E2F was released from the complex and bound to the TGF-β promoter region, resulting in TGF-β overexpression. Furthermore, the Smad4 signaling pathway was activated upon TGF-β overexpression, which led to an interaction between Smad4 and the miR-182 promoter region, subsequently inducing the upregulation of miR-182 in both cervical cancer cells and the surrounding normal cells. In conclusion, this newly identified high-risk HPV E7/TGF-β/miR-182 regulatory network might inform the development of specific therapeutic strategies for cervical cancer.
['Chen|Jiao|J|', 'Deng|Yan|Y|', 'Ao|Liangfei|L|', 'Song|Yi|Y|', 'Xu|Yan|Y|', 'Wang|Chi Chiu|CC|', 'Choy|Kwong Wai|KW|', 'Tony Chung|Kwok Hung|KH|', 'Du|Quan|Q|', 'Sui|Yi|Y|', 'Yang|Tao|T|', 'Yang|Jing|J|', 'Li|Hu|H|', 'Zou|Chang|C|', 'Tang|Tao|T|']
D000328:Adult D000818:Animals D001665:Binding Sites D018920:Coculture Techniques D004268:DNA-Binding Proteins D050684:E2F Transcription Factors D005260:Female D015972:Gene Expression Regulation, Neoplastic D006367:HeLa Cells D054884:Host-Pathogen Interactions D006801:Humans D008807:Mice, Inbred BALB C D008819:Mice, Nude D035683:MicroRNAs D008875:Middle Aged D009856:Oncogene Proteins, Viral D027383:Papillomaviridae D050725:Papillomavirus E7 Proteins D010766:Phosphorylation D011401:Promoter Regions, Genetic D016160:Retinoblastoma Protein D015398:Signal Transduction D051901:Smad4 Protein D016212:Transforming Growth Factor beta D015854:Up-Regulation D002583:Uterine Cervical Neoplasms
HPV miR-182 TGF-β Cervical cancer E7 oncogene