The expression of miR-21 and miR-143 is deregulated by the HPV16 E7 oncoprotein and 17β-estradiol.
MicroRNAs (miRNAs) are a class of non-coding RNAs that negatively regulate their target mRNAs at a posttranscriptional level, thereby affecting crucial processes in cancer development. However, little is known about the molecular events that control expression of miRNAs in cervical cancer (CC). HPV16 E7 oncoprotein in conjunction with estrogen are sufficient to produce high grade cervical dysplasia and invasive cervical malignancies in a mouse model. In the present study, we determined the potential role that the E7 oncoprotein and 17β-estradiol (E2) play in the deregulation of miR-21 and miR-143 expression levels by these two risk factors. We found that, while the expression of miR-21 was upregulated and the expression of miR-143 was downregulated by the HPV16 E7 oncoprotein in vivo, and in vitro and that E2 treatment is also implicated in the deregulation of these important miRNAs in vivo. Sustained upregulation of miR-21 resulted in suppression of PTEN expression, and repression of miR-143 increased the mRNA and protein levels from Bcl-2. These results suggested that HPV type 16 E7 oncoprotein and E2 play an important role in regulating miR-21 and miR-143 expression. We have observed similar results in CC patients containing HPV16 sequences, suggesting that these miRNAs could serve as diagnostic biomarkers in CC. The present study highlights the roles of miRNAs in cervical tissue and implicates these important molecules in cervical carcinogenesis.
Programa de Doctorado en Ciencias Biomédicas, Instituto de Fisiología Celular (IFC), Universidad Nacional Autónoma de México (UNAM), Ciudad de México 04510, Mexico.
Yazmín
Y
Gómez-Gómez
Programa de Doctorado en Ciencias Biomédicas, Instituto de Fisiología Celular (IFC), Universidad Nacional Autónoma de México (UNAM), Ciudad de México 04510, Mexico.
Jorge
J
Organista-Nava
Department of Genetics and Molecular Biology, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-IPN), Mexico city 07360, Mexico.
Rodolfo
R
Ocadiz-Delgado
Department of Genetics and Molecular Biology, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-IPN), Mexico city 07360, Mexico.
Enrique
E
García-Villa
Laboratory of Molecular Biomedicine, Academic Unit of Chemical-Biological Sciences, Guerrero State University, Chilpancingo 39090, Guerrero, Mexico.
Marco Antonio
MA
Leyva-Vazquez
Laboratory of Molecular Biomedicine, Academic Unit of Chemical-Biological Sciences, Guerrero State University, Chilpancingo 39090, Guerrero, Mexico.
Berenice
B
Illades-Aguiar
McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
Paul F
PF
Lambert
Cancer Biomedical Research Unit, National Cancer Institute and Biomedical Research Institute, Biomedical Research Institute, National Autonomous University of Mexico and Division of Basic Research, National Cancer Institute (INCan), Mexico city 14080, Mexico.
Alejandro
A
García-Carrancá
Department of Genetics and Molecular Biology, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-IPN), Mexico city 07360, Mexico.
Patricio
P
Gariglio
D000818:Animals; D045744:Cell Line, Tumor; D002584:Cervix Uteri / Q000187:drug effects / Q000378:metabolism / Q000502:physiology* / Q000821:virology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis / Q000235:genetics; D050725:Papillomavirus E7 Proteins / Q000008:administration & dosage* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology
C542359:MIRN143 microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D050725:Papillomavirus E7 Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C059731:oncogene protein E7, Human papillomavirus type 16; D004958:Estradiol; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human