Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\27602489
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Oncotarget
2016 ; 7
(40
): 64575-64588
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Piwil2 is reactivated by HPV oncoproteins and initiates cell reprogramming via
epigenetic regulation during cervical cancer tumorigenesis
#MMPMID27602489
Feng D
; Yan K
; Zhou Y
; Liang H
; Liang J
; Zhao W
; Dong Z
; Ling B
Oncotarget
2016[Oct]; 7
(40
): 64575-64588
PMID27602489
show ga
The human papillomavirus (HPV) oncoproteins E6 and E7 are risk factors that are
primarily responsible for the initiation and progression of cervical cancer, and
they play a key role in immortalization and transformation by reprogramming
differentiating host epithelial cells. It is unclear how cervical epithelial
cells transform into tumor-initiating cells (TICs). Here, we observed that the
germ stem cell protein Piwil2 is expressed in pre-cancerous and malignant lesions
of the cervix and cervical cancer cell lines with the exception of the
non-HPV-infected C33a cell line. Knockdown of Piwil2 by shRNA led to a marked
reduction in proliferation and colony formation, in vivo tumorigenicity,
chemo-resistance, and the proportion of cancer stem-like cells. In contrast,
Piwil2 overexpression induced malignant transformation of HaCaT cells and the
acquisition of tumor-initiating capabilities. Gene-set enrichment analysis
revealed embryonic stem cell (ESC) identity, malignant biological behavior, and
specifically, activation targets of the cell reprogramming factors c-Myc, Klf4,
Nanog, Oct4, and Sox2 in Piwil2-overexpressing HaCaT cells. We further confirmed
that E6 and E7 reactivated Piwil2 and that E6 and E7 overexpression resulted in a
similar gene-set enrichment pattern as Piwil2 overexpression in HaCaT cells.
Moreover, Piwil2 overexpression or E6 and E7 activation induced H3K9 acetylation
but reduced H3K9 trimethylation, which contributed to the epigenetic
reprogramming and ESC signature maintenance, as predicted previously. Our study
demonstrates that Piwil2, reactivated by the HPV oncoproteins E6 and E7, plays an
essential role in the transformation of cervical epithelial cells to TICs via
epigenetics-based cell reprogramming.