Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Nov 29:9:727217.
doi: 10.3389/fcell.2021.727217. eCollection 2021.

CRISPR/Cas9 in Gastrointestinal Malignancies

André Jefremow  1 , Markus F Neurath  1 , Maximilian J Waldner  1
Affiliations
Review

CRISPR/Cas9 in Gastrointestinal Malignancies

André Jefremow et al. Front Cell Dev Biol. .

Abstract

Gastrointestinal (GI) cancers such as colorectal cancer (CRC), gastric cancer (GC), esophageal cancer (EG), pancreatic duct adenocarcinoma (PDAC) or hepatocellular cancer (HCC) belong to the most commonly diagnosed types of cancer and are among the most frequent causes of cancer related death worldwide. Most types of GI cancer develop in a stepwise fashion with the occurrence of various driver mutations during tumor progression. Understanding the precise function of mutations driving GI cancer development has been regarded as a prerequisite for an improved clinical management of GI malignancies. During recent years, CRISPR/Cas9 has developed into a powerful tool for genome editing in cancer research by knocking in and knocking out even multiple genes at the same time. Within this review, we discuss recent applications for CRISPR/Cas9-based genome editing in GI cancer research including CRC, GC, EG, PDAC and HCC. These applications include functional studies of candidate genes in cancer cell lines or organoids in vitro as well as in murine cancer models in vivo, library screening for the identification of previously unknown driver mutations and even gene therapy of GI cancers.

Keywords: CRISPR/cas9; cancer of the biliary tract; colorectal cancer; esophageal cancer; gastrointestinal cancer; hepatocellular cancer; pancreatic cancer.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Mechanism of CRISPR/Cas9. The single guide (sg) RNA (target sequence in blue) is directed to the target site in the genomic DNA of the host. The Cas9 endonuclease forms a complex with the sgRNA and binds to the complementary DNA region upstream of the protospacer-adjacent motif (PAM). The Cas9 nuclease then cleaves both DNA strands about 3 base pairs upstream of the PAM. Repair of this DNA double-strand break either occurs through non-homologous end joining (NHEJ) or homology-directed repair (HDR). As NHEJ frequently induces insertions or deletions, this pathway results in a knock-out of the target gene. In contrast, HDR requires a donor DNA template, which will be inserted into the host DNA. Therefore, HDR can be used for knock-in applications (adopted from Moses et al., 2018 and Zhan et al., 2019).
See this image and copyright information in PMC

References

    1. Abudureheman A., Ainiwaer J., Hou Z., Niyaz M., Turghun A., Hasim A., et al. (2018). High MLL2 Expression Predicts Poor Prognosis and Promotes Tumor Progression by Inducing EMT in Esophageal Squamous Cell Carcinoma. J. Cancer Res. Clin. Oncol. 144, 1025–1035. 10.1007/s00432-018-2625-5 - DOI - PMC - PubMed
    1. Ardelt M. A., Fröhlich T., Martini E., Müller M., Kanitz V., Atzberger C., et al. (2019). Inhibition of Cyclin-Dependent Kinase 5: A Strategy to Improve Sorafenib Response in Hepatocellular Carcinoma Therapy. Hepatology 69, 376–393. 10.1002/hep.30190 - DOI - PMC - PubMed
    1. Armacki M., Polaschek S., Waldenmaier M., Morawe M., Ruhland C., Schmid R., et al. (2020). Protein Kinase D1, Reduced in Human Pancreatic Tumors, Increases Secretion of Small Extracellular Vesicles from Cancer Cells that Promote Metastasis to Lung in Mice. Gastroenterology 159, 1019–1035. e1022. 10.1053/j.gastro.2020.05.052 - DOI - PubMed
    1. Bao M. H.-R., Yang C., Tse A. P.-W., Wei L., Lee D., Zhang M. S., et al. (2021). Genome-Wide CRISPR-Cas9 Knockout Library Screening Identified PTPMT1 in Cardiolipin Synthesis Is Crucial to Survival in Hypoxia in Liver Cancer. Cel. Rep. 34, 108676. 10.1016/j.celrep.2020.108676 - DOI - PubMed
    1. Barrangou R., Doudna J. A. (2016). Applications of CRISPR Technologies in Research and beyond. Nat. Biotechnol. 34, 933–941. 10.1038/nbt.3659 - DOI - PubMed