Perturbation of DROSHA and DICER expression by human papillomavirus 16 oncoproteins

Mallory E Harden; Karl Munger

doi:10.1016/j.virol.2017.04.022

Perturbation of DROSHA and DICER expression by human papillomavirus 16 oncoproteins

Virology. 2017 Jul:507:192-198. doi: 10.1016/j.virol.2017.04.022. Epub 2017 Apr 24.

Authors

Mallory E Harden¹, Karl Munger²

Affiliations

¹ Program in Virology, Division of Medical Sciences, Harvard Medical School Boston, MA 02115, USA; Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111, USA.
² Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111, USA. Electronic address: karl.munger@tufts.edu.

Abstract

Many tumors, including cervical carcinoma, show dysregulated expression of the microRNA processing machinery, specifically DROSHA and DICER. Some cervical cancers exhibit chromosome 5p amplifications and DROSHA is the most significantly upregulated transcript and is observed in all tumors with 5p gain. DROSHA and DICER mRNA levels, however, are higher in HPV positive cancer lines than in an HPV negative cervical carcinoma line. We show that high-risk HPV E6/E7 expression in HPV negative C33A cervical carcinoma cells and primary human epithelial cell causes increased expression of DROSHA and DICER mRNA and protein. Most importantly, many DROSHA regulated microRNAs are dysregulated in HPV16 E6/E7 expressing cells. These results suggest that increased DROSHA levels contribute to HPV16 E6/E7 dysregulation of cellular microRNA expression.

Keywords: Cervical cancer; Human papillomavirus; microRNA.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

DEAD-box RNA Helicases / genetics*
DEAD-box RNA Helicases / metabolism
Female
Gene Expression Regulation, Neoplastic
Human papillomavirus 16 / genetics
Human papillomavirus 16 / metabolism*
Humans
MicroRNAs / genetics
MicroRNAs / metabolism
Oncogene Proteins, Viral / genetics
Oncogene Proteins, Viral / metabolism*
Papillomavirus E7 Proteins / genetics
Papillomavirus E7 Proteins / metabolism*
Papillomavirus Infections / genetics*
Papillomavirus Infections / metabolism
Papillomavirus Infections / virology
Repressor Proteins / genetics
Repressor Proteins / metabolism*
Ribonuclease III / genetics*
Ribonuclease III / metabolism
Uterine Cervical Neoplasms / genetics*
Uterine Cervical Neoplasms / metabolism
Uterine Cervical Neoplasms / virology

Substances

E6 protein, Human papillomavirus type 16
MicroRNAs
Oncogene Proteins, Viral
Papillomavirus E7 Proteins
Repressor Proteins
oncogene protein E7, Human papillomavirus type 16
DICER1 protein, human
DROSHA protein, human
Ribonuclease III
DEAD-box RNA Helicases

Abstract

Publication types

MeSH terms

Substances

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