In vitro and in vivo growth suppression of human papillomavirus 16-positive cervical cancer cells by CRISPR/Cas9
Abstract
Deregulated expression of high-risk human papillomavirus oncogenes (E6 and E7) is a pivotal event for pathogenesis and progression in cervical cancer. Both viral oncogenes are therefore regarded as ideal therapeutic targets. In the hope of developing a gene-specific therapy for HPV-related cancer, we established CRISPR/Cas9 targeting promoter of HPV 16 E6/E7 and targeting E6, E7 transcript, transduced the CRISPR/Cas9 into cervical HPV-16-positive cell line SiHa. The results showed that CRISPR/Cas9 targeting promoter, as well as targeting E6 and E7 resulted in accumulation of p53 and p21 protein, and consequently remarkably reduced the abilities of proliferation of cervical cancer cells in vitro. Then we inoculated subcutaneously cells into nude mice to establish the transplanted tumor animal models, and found dramatically inhibited tumorigenesis and growth of mice incubated by cells with CRISPR/Cas9 targeting (promoter+E6+E7)-transcript. Our results may provide evidence for application of CRISPR/Cas9 targeting HR-HPV key oncogenes, as a new treatment strategy, in cervical and other HPV-associated cancer therapy.
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Zhen et al reported that transfection of Cas9 and sgRNAs targeting HPV16 E6 or E7 into HPV-16-positive cervical carcinoma cell lines SiHa resulted in inhibition of cancer cell proliferation in vitro and in a xenograft mouse model.
“Zhen et al 41 reported that the transfection of Cas9 and sgRNAs targeting HPV16 E6 or E7 into HPV-16-positive cervical carcinoma cell lines SiHa resulted in the inhibition of cancer cell proliferation both in vitro and in xenograft mouse model.”
From CRISPR-Cas9: a new and promising player in gene therapy (2015) · cites this paper as [41]
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CRISPR-Cas9: a new and promising player in gene therapy
Xiao-Jie, L., Hui-Ying, X., Zun-Ping, K., Jin-Lian, C., & Li-Juan, J. (2015) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2014-102968 · Cited by 200 · see citing works
- Authors
- Zhen, S., Hua, L., Takahashi, Y., Narita, S., Liu, Y.-H., & Li, Y.
- Affiliations
- Kyoto University (JP)
- Corresponding author
- Zhen, Shuai
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 450
- Issue
- 4
- Pages
- 1422-1426
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W1979954728
- Semantic Scholar
- c18ef9fe844f241f8c0ec4c5f9db885600450a69
- Cited by
- 219
- References
- 38
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 19 · 2023: 13 · 2022: 19 · 2021: 24 · 2020: 21 · 2019: 17 · 2018: 30 · 2017: 21 · 2016: 22 · 2015: 16 · 2014: 2
- FWCI
- 8.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Massachusetts Institute of Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- CRISPR/Cas9, HPV16, cervical cancer, HPV E6 oncogene, HPV E7 oncogene, gene-specific therapy, promoter targeting, p53, p21, cell proliferation inhibition, carcinogenesis, SiHa cells, HPV-associated cancers
- MeSH terms
- Base Sequence, Cell Division, Uterine Cervical Neoplasms, Female, Humans, DNA Primers, Cell Line, Tumor, Alphapapillomavirus, Clustered Regularly Interspaced Short Palindromic Repeats, In Vitro Techniques
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