E6 and E7 gene silencing results in decreased methylation of tumor suppressor genes and induces phenotype transformation of human cervical carcinoma cell lines

Oncotarget
Liming LiMingjun Jiang

Abstract

In SiHa and CaSki cells, E6 and E7-targeting shRNA specifically and effectively knocked down human papillomavirus (HPV) 16 E6 and E7 at the transcriptional level, reduced the E6 and E7 mRNA levels by more than 80% compared with control cells that expressed a scrambled-sequence shRNA. E6 and E7 repression resulted in down-regulation of DNA methyltransferase mRNA and protein expression, decreased DNA methylation and increased mRNA expression levels of tumor suppressor genes, induced a certain apoptosis and inhibited proliferation in E6 and E7 shRNA-infected SiHa and CaSki cells compared with the uninfected cells. Repression of E6 and E7 oncogenes resulted in restoration of DNA methyltransferase suppressor pathways and induced apoptosis in HPV16-positive cervical carcinoma cell lines. Our findings suggest that the potential carcinogenic mechanism of HPV16 through influencing DNA methylation pathway to activate the development of cervical cancer exist, and maybe as a candidate therapeutic strategy for cervical and other HPV-associated cancers.

References

Sep 3, 1996·Proceedings of the National Academy of Sciences of the United States of America·J G HermanS B Baylin
Mar 29, 2000·Nucleic Acids Research·C A EadsP W Laird
May 18, 2001·Nature·G I Evan, K H Vousden
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
Jun 28, 2002·Nature·Jean-Marc JacqueMario Stevenson
Oct 23, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·John CapodiciDrew Weissman
Jan 31, 2003·British Journal of Cancer·G M CliffordS Franceschi
Apr 3, 2003·Nature Reviews. Cancer·Peter W Laird
Nov 6, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·Mitsuo YoshinouchiKenji Yamato
Sep 17, 2004·Nature·Gregory J Hannon, John J Rossi
Dec 28, 2004·Nature Medicine·Vira BitkoSailen Barik
Mar 12, 2005·CA: a Cancer Journal for Clinicians·D Max ParkinPaola Pisani
Jan 26, 2006·BMC Biotechnology·Debra J TaxmanWilliam Reed
Jan 26, 2006·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Pavel SovaNancy Kiviat
Jun 30, 2006·Nucleic Acids Research·Richard J ShawTriantafillos Liloglou
Jul 29, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Scot D HenryLuc J W van der Laan
Sep 9, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Olivier ter BrakeBen Berkhout
Sep 20, 2006·Oncogene·W A BurgersF Fuks
Nov 9, 2006·Proceedings of the National Academy of Sciences of the United States of America·Bruce L LevineCarl H June
Mar 21, 2007·Biochimica Et Biophysica Acta·Victor V Levenson
May 1, 2007·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·D HongX Xie
Jan 9, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Olivier ter BrakeBen Berkhout
Mar 12, 2009·Journal of the National Cancer Institute·Theodore RampiasAmanda Psyrri
May 7, 2009·Human Mutation·Rolf H A M VossenJohan T den Dunnen
Jan 19, 2011·Chembiochem : a European Journal of Chemical Biology·Renata Zofia JurkowskaAlbert Jeltsch
Dec 14, 2011·Oncology Reports·Aggeliki TsergaAngelica A Saetta
Feb 28, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Stéphanie BougelJean Benhattar

❮ Previous
Next ❯

Citations

Aug 7, 2018·Epigenetics : Official Journal of the DNA Methylation Society·Wina VerlaatG Bea A Wisman
Jun 23, 2020·Oncology Letters·Pattamawadee YanatatsaneejitApiwat Mutirangura
Sep 17, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Asel BiktasovaNatalia Issaeva
Feb 2, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·M K SannigrahiMadhu Khullar
Feb 21, 2019·Acta Cytologica·Anna PaasoKarolina Louvanto

❮ Previous
Next ❯

Methods Mentioned

BETA
electrophoresis
flow cytometry
PCR
Knockdown
transfection
Protein Assay

Software Mentioned

MethyLight
MFOLD
BLAST
SPSS16
viia

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis