Dependence of intracellular and exosomal microRNAs on viral E6/E7 oncogene expression in HPV-positive tumor cells

PLoS Pathogens
Anja HoneggerF Hoppe-Seyler

Abstract

Specific types of human papillomaviruses (HPVs) cause cervical cancer. Cervical cancers exhibit aberrant cellular microRNA (miRNA) expression patterns. By genome-wide analyses, we investigate whether the intracellular and exosomal miRNA compositions of HPV-positive cancer cells are dependent on endogenous E6/E7 oncogene expression. Deep sequencing studies combined with qRT-PCR analyses show that E6/E7 silencing significantly affects ten of the 52 most abundant intracellular miRNAs in HPV18-positive HeLa cells, downregulating miR-17-5p, miR-186-5p, miR-378a-3p, miR-378f, miR-629-5p and miR-7-5p, and upregulating miR-143-3p, miR-23a-3p, miR-23b-3p and miR-27b-3p. The effects of E6/E7 silencing on miRNA levels are mainly not dependent on p53 and similarly observed in HPV16-positive SiHa cells. The E6/E7-regulated miRNAs are enriched for species involved in the control of cell proliferation, senescence and apoptosis, suggesting that they contribute to the growth of HPV-positive cancer cells. Consistently, we show that sustained E6/E7 expression is required to maintain the intracellular levels of members of the miR-17~92 cluster, which reduce expression of the anti-proliferative p21 gene in HPV-positive cancer cells. In exosomes sec...Continue Reading

References

Dec 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·J Settleman, D DiMaio
Aug 1, 1987·Molecular and Cellular Biology·C Chen, H Okayama
Dec 1, 1995·Journal of Virology·J J DowhanickP M Howley
Sep 26, 1995·Proceedings of the National Academy of Sciences of the United States of America·G P DimriO Pereira-Smith
Nov 19, 1993·Cell·W S el-DeiryB Vogelstein
Mar 6, 1998·Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al]·H P RutzR O Mirimanoff
Jun 1, 2000·Proceedings of the National Academy of Sciences of the United States of America·K ButzF Hoppe-Seyler
Sep 27, 2000·Proceedings of the National Academy of Sciences of the United States of America·E C GoodwinE S Hwang
Nov 9, 2000·Proceedings of the National Academy of Sciences of the United States of America·E C Goodwin, D DiMaio
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jun 5, 2002·Nature Reviews. Cancer·Harald zur Hausen
Apr 30, 2003·Journal of Virology·Allison H S Hall, Kenneth A Alexander
Dec 19, 2003·Nucleic Acids Research·Sam Griffiths-Jones
Jun 10, 2005·Nature·Jun LuTodd R Golub
Jun 10, 2005·Nature·Kathryn A O'DonnellJoshua T Mendell
Dec 6, 2005·Journal of Molecular Biology·Heather GriffinJohn Doorbar
Dec 31, 2005·Nucleic Acids Research·Sam Griffiths-JonesAnton J Enright
Jan 27, 2006·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Irena Crnković-MertensKarin Butz
Mar 15, 2006·Cancer Cell·Nozomu YanaiharaCurtis C Harris
Jan 6, 2007·The British Journal of Surgery·B P L WijnhovenD I Watson
Jun 26, 2007·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Ruprecht KunerFelix Hoppe-Seyler
Jul 10, 2007·Cancer Research·Weng-Onn LuiAndrew Fire
Jul 31, 2007·Biochemical and Biophysical Research Communications·Magali LagrangeFrançois Deryckere
Nov 10, 2007·Nucleic Acids Research·Sam Griffiths-JonesAnton J Enright
Nov 29, 2007·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Jack B CowlandKirsten Grønbaek
Dec 14, 2007·Proceedings of the National Academy of Sciences of the United States of America·Daniel Y LeeBurton B Yang
Jan 30, 2008·Current Protocols in Cell Biology·Clotilde ThéryAled Clayton
May 3, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jeong-Won LeeDuk-Soo Bae
Jul 1, 2008·Gynecologic Oncology·Douglas D Taylor, Cicek Gercel-Taylor
Aug 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·John A FoekensJohn W M Martens
Nov 15, 2008·Virology·Margaret E McLaughlin-Drubin, Karl Münger

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Citations

Aug 27, 2015·Journal of Clinical Medicine·Jessica L HorshamPeter J Leedman
Aug 22, 2015·Viruses·Sonia AssilMarlène Dreux
Sep 24, 2015·Viruses·Marta Alenquer, Maria João Amorim
Nov 8, 2015·The International Journal of Biochemistry & Cell Biology·Jessica L HorshamPeter J Leedman
Mar 30, 2016·Cytokine & Growth Factor Reviews·Giorgio ManginoGiovanna Romeo
Apr 5, 2016·Veterinary and Comparative Oncology·N Terron-CanedoL Nasir
Oct 29, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Shweta SharmaMausumi Bharadwaj
Jun 15, 2016·Journal of Cancer Research and Clinical Oncology·Maria Vincenza ChiantoreGiovanna Romeo
Jan 25, 2017·Proceedings of the National Academy of Sciences of the United States of America·Karin Hoppe-SeylerFelix Hoppe-Seyler
Jan 31, 2017·International Journal of Immunopathology and Pharmacology·Li-Dan Hou, Jing Zhang
Mar 30, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Li DingJinhai Tang
Jul 6, 2017·Viruses·Karin Hoppe-SeylerFelix Hoppe-Seyler
Jul 27, 2018·PLoS Pathogens·Rachel ChirayilChristopher S Sullivan
Sep 22, 2016·MBio·Elizabeth A WhitePeter M Howley
Sep 24, 2018·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Ben PeacockStuart Hunt
Sep 9, 2017·PloS One·David J SchultzCarolyn M Klinge
Nov 4, 2016·G3 : Genes - Genomes - Genetics·Emily K TsangStephen B Montgomery
Jun 22, 2016·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Monique R AndersonSteven Jacobson
Sep 12, 2019·Scientific Reports·Sirisha ThippabhotlaMei He
Nov 27, 2019·Biomolecules·Laith N Al-EitanFiras A Al-Qarqaz
Mar 4, 2020·Cancers·Sudipta PathakEdyta Paradowska
Apr 9, 2019·Epigenetics : Official Journal of the DNA Methylation Society·Iris BabionRenske D M Steenbergen
May 1, 2020·Journal of Biomolecular Structure & Dynamics·Raied A BadierahElrashdy M Redwan
May 8, 2020·Cancer Biotherapy & Radiopharmaceuticals·Xi PanPei-Guo Cao
Jan 2, 2018·Oncotarget·Karin Hoppe-SeylerFelix Hoppe-Seyler
Jun 20, 2020·PloS One·Alexandra FullárIlona Kovalszky
Sep 23, 2020·Epigenomics·Javid Sadri NahandHamed Mirzaei

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Methods Mentioned

BETA
biopsies
transfection
electron microscopy
lavages
transfections
fluorescence-activated cell sorting
Protein Assay
Reverse Transcription-PCR
PCR
electrophoresis

Software Mentioned

FlowJo
miRDeep2 package
CellQuest Pro
Sigma Plot
7300 System SDS
BioID
miRDeep2

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