Two less common human microRNAs miR-875 and miR-3144 target a conserved site of E6 oncogene in most high-risk human papillomavirus subtypes.
Human papillomaviruses (HPVs) including high-risk (HR) and low-risk (LR) subtypes have distinguishable variation on both genotypes and phenotypes. The co-infection of multiple HR-HPVs, headed by HPV16, is common in cervical cancer in female. Recently accumulating reports have focused on the interaction between virus and host, particularly the role of human microRNAs (miRNAs) in anti-viral defense by targeting viral genome. Here, we found a well-conserved target site of miRNAs in the genomes of most HR-HPVs, not LR-HPVs, by scanning all potential target sites of human miRNAs on 24 HPVs of unambiguous subtypes of risk. The site is targeted by two less common human miRNAs, miR-875 and miR-3144, and is located in E6 oncogene open reading frame (ORF) and overlap with the first alternative splice exon of viral early transcripts. In validation tests, miR-875 and miR-3144 were identified to suppress the target reporter activity markedly and inhibit the expression of both synthetically exogenous E6 and endogenous E6 oncogene. High level of two miRNAs can inhibit cell growth and promote apoptosis in HPV16-positive cervical cancer cells. This study provides a promising common target of miRNAs for most HR-HPVs and highlights the effects of two low expressed human miRNAs on tumour suppression.
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011 China.
Lin
L
Lin
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011 China.|Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011 China.
Qingqing
Q
Cai
School of Life Sciences and Technology, Tongji University, Shanghai, 200092 China.
Xiaoyan
X
Zhang
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011 China.
Hongwei
H
Zhang
Shanghai Center for Bioinformation Technology, Shanghai, 200235 China.|School of Life Sciences, Fudan University, Shanghai, 200433 China.
Yang
Y
Zhong
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011 China.|Department of Obstetrics and Gynecology of Shanghai Medical School, Fudan University, Shanghai, 200032 China.|Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011 China.|Institute of Biomedical Sciences, Fudan University, Shanghai, 200032 China.
Congjian
C
Xu
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011 China.
Yanyun
Y
Li
D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015870:Gene Expression; D054884:Host-Pathogen Interactions / Q000235:genetics; D052162:Human papillomavirus 16 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology
C068651:E6 protein, Human papillomavirus type 16; C000606834:MIRN-3144 microRNA, human; C000606835:MIRN-875 microRNA, human; D035683:MicroRNAs; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins