CDH1 and SNAI1 are regulated by E7 from human papillomavirus types 16 and 18
Por:
Rosendo-Chalma, Pedro, Antonio-Vejar, Veronica, Bigoni-Ordonez, Gabriele Davide, Patino-Morales, Carlos Cesar, Cano-Garcia, Amparo, Garcia-Carranca, Alejandro
Publicada:
1 jul 2020
Resumen:
A common characteristic of cancer types associated with viruses is the
dysregulated expression of theCDH1gene, which encodes E-cadherin, in
general by activation of DNA methyltransferases (Dnmts). In cervical
cancer, E7 protein from high risk human papillomaviruses (HPVs) has been
demonstrated to interact with Dnmt1 and histone deacetylase type 1
(HDAC1). The present study proposed that E7 may regulate the expression
ofCDH1through two pathways: i) Epigenetic, including DNA methylation;
and ii) Epigenetic-independent, including the induction of negative
regulators ofCDH1expression, such as Snail family transcriptional
repressor Snai1 and Snai2. To test this hypothesis, HPV16- and
HPV18-positive cell lines were used to determine the methylation pattern
of theCDH1promoter and its expression in association with its negative
regulators. Different methylation frequencies were identified in
theCDH1promoter in HeLa (88.24%) compared with SiHa (17.65%) and Ca
Ski (0%) cell lines. Significant differences in the expression
ofSNAI1were observed between these cell lines, and an inverse
association was identified between the expression levels ofSNAI1andCDH1.
In addition, suppressing E7 not only increased the expression ofCDH1,
but notably decreased the expression ofSNAI1and modified the methylation
pattern of theCDH1promoter. These results suggested that the expression
ofCDH1was dependent on the expression ofSNAI1and was inversely
associated with the expression of E7. The present results indicated that
E7 from HPV16/18 regulated the expression ofCDH1by the two following
pathways in which Snai1 is involved: i) Hypermethylation of
theCDH1promoter region and increasing expression ofSNAI1, as observed in
HeLa; and ii) Hypomethylation of theCDH1promoter region and expression
ofSNAI1, as observed in SiHa. Therefore, the suppression ofCDH1and
expression ofSNAI1may be considered to be biomarkers of metastasis in
uterine cervical cancer.
Filiaciones:
Rosendo-Chalma, Pedro:
Univ Nacl Autonoma Mexico, Inst Invest Biomed IIB, Programa Doctorado Ciencias Biomed, Mexico City 10450, DF, Mexico
Univ Nacl Autonoma Mexico IIB UNAM, Inst Invest Biomed, Unidad Invest Biomed Canc, Lab Virus & Canc, Mexico City 14080, DF, Mexico
Inst Nacl Cancerol Secretaria Salud INCan SSA, Div Invest Basica, Mexico City 14080, DF, Mexico
Antonio-Vejar, Veronica:
Univ Nacl Autonoma Mexico IIB UNAM, Inst Invest Biomed, Unidad Invest Biomed Canc, Lab Virus & Canc, Mexico City 14080, DF, Mexico
Inst Nacl Cancerol Secretaria Salud INCan SSA, Div Invest Basica, Mexico City 14080, DF, Mexico
Univ Autonoma Guerrero UAGro, Unidad Acad Ciencias Quimico Biol UACQB, Lab Biomed Mol, Chilpancingo 39090, Guerrero, Mexico
Bigoni-Ordonez, Gabriele Davide:
Univ Nacl Autonoma Mexico IIB UNAM, Inst Invest Biomed, Unidad Invest Biomed Canc, Lab Virus & Canc, Mexico City 14080, DF, Mexico
Inst Nacl Cancerol Secretaria Salud INCan SSA, Div Invest Basica, Mexico City 14080, DF, Mexico
Patino-Morales, Carlos Cesar:
Univ Nacl Autonoma Mexico IIB UNAM, Inst Invest Biomed, Unidad Invest Biomed Canc, Lab Virus & Canc, Mexico City 14080, DF, Mexico
Inst Nacl Cancerol Secretaria Salud INCan SSA, Div Invest Basica, Mexico City 14080, DF, Mexico
Cano-Garcia, Amparo:
Univ Autonoma Madrid UAM, Hosp Univ La Paz IdiPAZ, Inst Invest Sanitaria, Inst Invest Biomed Alberto Sols CSIC UAM,Dept Bio, Madrid, Spain
Ctr Invest Biomed Red Canc CIBERONC, Madrid 28029, Spain
Garcia-Carranca, Alejandro:
Univ Nacl Autonoma Mexico IIB UNAM, Inst Invest Biomed, Unidad Invest Biomed Canc, Lab Virus & Canc, Mexico City 14080, DF, Mexico
Inst Nacl Cancerol Secretaria Salud INCan SSA, Div Invest Basica, Mexico City 14080, DF, Mexico
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