Journal Article

DKFZ-2019-01014

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Folate Repletion after Deficiency Induces Irreversible Genomic and Transcriptional Changes in Human Papillomavirus Type 16 (HPV16)-Immortalized Human Keratinocytes.

Savini, C. (First author)DKFZ* ; Yang, R. (First author)DKFZ* ; Savelyeva, L.DKFZ* ; Göckel-Krzikalla, E.DKFZ* ; Hotz-Wagenblatt, A.DKFZ* ; Westermann, F.DKFZ* ; Rösl, F. (Last author)DKFZ*

2019
Molecular Diversity Preservation International Basel

This record in other databases:  

Please use a persistent id in citations: doi:10.3390/ijms20051100

Abstract: Supplementation of micronutrients like folate is a double-edged sword in terms of their ambivalent role in cell metabolism. Although several epidemiological studies support a protective role of folate in carcinogenesis, there are also data arguing for an opposite effect. To address this issue in the context of human papillomavirus (HPV)-induced transformation, the molecular events of different folate availability on human keratinocytes immortalized by HPV16 E6 and E7 oncoproteins were examined. Several sublines were established: Control (4.5 µM folate), folate deficient (0.002 µM folate), and repleted cells (4.5 µM folate). Cells were analyzed in terms of oncogene expression, DNA damage and repair, karyotype changes, whole-genome sequencing, and transcriptomics. Here we show that folate depletion irreversibly induces DNA damage, impairment of DNA repair fidelity, and unique chromosomal alterations. Repleted cells additionally underwent growth advantage and enhanced clonogenicity, while the above mentioned impaired molecular properties became even more pronounced. Overall, it appears that a period of folate deficiency followed by repletion can shape immortalized cells toward an anomalous phenotype, thereby potentially contributing to carcinogenesis. These observations should elicit questions and inquiries for broader additional studies regarding folate fortification programs, especially in developing countries with micronutrient deficiencies and high HPV prevalence.

Note: #DKFZ-MOST-Ca182#

---

Contributing Institute(s):

1. Virale Transformationsmechanismen (F030)
2. B087 Neuroblastom Genomik (B087)
3. Bioinformatik (HUSAR) (W180)

Research Program(s):

1. 316 - Infections and cancer (POF3-316) (POF3-316)

Appears in the scientific report 2019

---

Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---