scholarly journals Metabolic rewiring is associated with HPV-specific profiles in cervical cancer cell lines

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kalliopi I. Pappa ◽  
George Daskalakis ◽  
Nicholas P. Anagnou
Keyword(s):  
Cervical Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
High Resolution Mass Spectrometry ◽  
Cancer Cell Lines ◽  
Ultra Performance Liquid Chromatography ◽  
Hpv E6 ◽  
Cervical Cell ◽  
E6 Protein

AbstractBoth HPV-positive and HPV-negative cervical cancers are associated with aberrant metabolism, although the oncogenic drivers remain elusive. Here we show the assessment of the metabolomic profiles of four distinct cervical cell lines, a normal and three cancer cell lines, one HPV-negative (C33A) and two HPV-positive (SiHa HPV16+, HeLa HPV18+), employing an ultra performance liquid chromatography and a high resolution mass spectrometry. Out of the total 462 metabolites, 248 to 326 exhibited statistically significant differences, while Random Forests analysis identified unique molecules for each cell line. The two HPV+ cell lines exhibited features of Warburg metabolism, consistent with the role of the HPV E6 protein. SiHa and HeLa cells displayed purine salvage pathway activity, while C33A cells revealed synthesis of cytidine, via a novel mechanism. These data document a highly dynamic HPV-specific rewiring of metabolic pathways occurring in cervical cancer. Therefore, this approach can eventually provide novel mechanistic insights into cervical carcinogenesis.

scholarly journals 49P Role of microRNAs in a panel of human cervical cancer cell lines

2020 ◽  
Vol 31 ◽  
pp. S259
Author(s):  
R.L. Causin ◽  
M.R. Nunes ◽  
L.S. da Silva ◽  
A.J.A. de Freitas ◽  
A.C. Carvalho ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Cervical Cancer Cell ◽  
Human Cervical Cancer Cell ◽  
Human Cervical Cancer

Sensitization of cervical cancer cell lines to low-dose radiation by retinoic acid does not require functional p53

2005 ◽  
Vol 97 (1) ◽  
pp. 142-150 ◽  
Author(s):  
Todd D. Tillmanns ◽  
Scott A. Kamelle ◽  
Suresh Guruswamy ◽  
Natalie S. Gould ◽  
Teresa L. Rutledge ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Retinoic Acid ◽  
Cell Lines ◽  
Cancer Cell ◽  
Low Dose ◽  
Cancer Cell Lines ◽  
Cervical Cancer Cell ◽  
Low Dose Radiation ◽  
Dose Radiation

scholarly journals Adenoviral Vectors Armed with PAPILLOMAVIRUs Oncogene Specific CRISPR/Cas9 Kill Human-Papillomavirus-Induced Cervical Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1934 ◽  
Author(s):  
Eric Ehrke-Schulz ◽  
Sonja Heinemann ◽  
Lukas Schulte ◽  
Maren Schiwon ◽  
Anja Ehrhardt
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Adenoviral Vectors ◽  
Human Papillomaviruses ◽  
Cervical Cancer Cell ◽  
Adenoviral Delivery ◽  
Cervical Cancer Cells

Human papillomaviruses (HPV) cause malignant epithelial cancers including cervical carcinoma, non-melanoma skin and head and neck cancer. They drive tumor development through the expression of their oncoproteins E6 and E7. Designer nucleases were shown to be efficient to specifically destroy HPV16 and HPV18 oncogenes to induce cell cycle arrest and apoptosis. Here, we used high-capacity adenoviral vectors (HCAdVs) expressing the complete CRISPR/Cas9 machinery specific for HPV18-E6 or HPV16-E6. Cervical cancer cell lines SiHa and CaSki containing HPV16 and HeLa cells containing HPV18 genomes integrated into the cellular genome, as well as HPV-negative cancer cells were transduced with HPV-type-specific CRISPR-HCAdV. Upon adenoviral delivery, the expression of HPV-type-specific CRISPR/Cas9 resulted in decreased cell viability of HPV-positive cervical cancer cell lines, whereas HPV-negative cells were unaffected. Transduced cervical cancer cells showed increased apoptosis induction and decreased proliferation compared to untreated or HPV negative control cells. This suggests that HCAdV can serve as HPV-specific cancer gene therapeutic agents when armed with HPV-type-specific CRISPR/Cas9. Based on the versatility of the CRISPR/Cas9 system, we anticipate that our approach can contribute to personalized treatment options specific for the respective HPV type present in each individual tumor.

scholarly journals The application of CRISPR/Cas9 system in cervical carcinogenesis

2021 ◽  
Author(s):  
Chun Gao ◽  
Ping Wu ◽  
Lan Yu ◽  
Liting Liu ◽  
Hong Liu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Transgenic Mice ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Precancerous Lesions ◽  
Cancer Cell Lines ◽  
Cervical Carcinogenesis ◽  
Cervical Precancerous Lesions

AbstractIntegration of high-risk HPV genomes into cellular chromatin has been confirmed to promote cervical carcinogenesis, with HPV16 being the most prevalent high-risk type. Herein, we evaluated the therapeutic effect of the CRISPR/Cas9 system in cervical carcinogenesis, especially for cervical precancerous lesions. In cervical cancer/pre-cancer cell lines, we transfected the HPV16 E7 targeted CRISPR/Cas9, TALEN, ZFN plasmids, respectively. Compared to previous established ZFN and TALEN systems, CRISPR/Cas9 has shown comparable efficiency and specificity in inhibiting cell growth and colony formation and inducing apoptosis in cervical cancer/pre-cancer cell lines, which seemed to be more pronounced in the S12 cell line derived from the low-grade cervical lesion. Furthermore, in xenograft formation assays, CRISPR/Cas9 inhibited tumor formation of the S12 cell line in vivo and affected the corresponding protein expression. In the K14-HPV16 transgenic mice model of HPV-driven spontaneous cervical carcinogenesis, cervical application of CRISPR/Cas9 treatment caused mutations of the E7 gene and restored the expression of RB, E2F1, and CDK2, thereby reversing the cervical carcinogenesis phenotype. In this study, we have demonstrated that CRISPR/Cas9 targeting HPV16 E7 could effectively revert the HPV-related cervical carcinogenesis in vitro, as well as in K14-HPV16 transgenic mice, which has shown great potential in clinical treatment for cervical precancerous lesions.

Sign in / Sign up

Export Citation Format

Share Document