CRISPR Screening Identifies Important Tumor Suppressor Genes

Using gene editing to systematically screen a large number of tumor suppressor genes, researchers in China have identified five genes linked to lung tumor growth.

AsianScientist (Apr. 20, 2018) – CRISPR/Cas9 gene editing has enabled researchers in China to perform a systematic screen of more than 50 tumor suppressor genes and identify five of them that are particularly important in lung cancer. These results have been published in the Proceedings of the National Academy of Science.

Cancer genomic studies have identified thousands of potentially important tumor suppressor genes. However, with the exception of a few well-studied genes, most of these genetic aberrations remain to be functionally validated and characterized.

In the present study, a team led by Dr. Ji Hongbin at the Shanghai Institute of Biochemistry and Cell Biology of Chinese Academy of Sciences and Dr. Chen Liang at the Institute of Life and Health Engineering, Jinan University, used CRISPR/Cas9 gene editing to systematically screen tumor suppressor genes in vivo.

The researchers first knocked down 55 tumor suppressor gene candidates one by one in mice, identifying five genes that contribute to malignant lung cancer. These five genes—Utx, Ptip, Acp5, Acacb and Clu—are also frequently down-regulated in human lung cancer specimens and significantly associated with lung cancer patient survival.

Importantly, the researchers found that tumorigenesis was accelerated when Utx was knocked out in a mouse model of lung cancer. However, a compound called JQEZ5 was able to supress the growth of lung tumors in Utx-knockout mice, suggesting that the drug might also be useful in treating human lung cancer patients with low UTX levels.

The article can be found at Wu et al. (2018) In vivo CRISPR Screening Unveils Histone Demethylase UTX as an Important Epigenetic Regulator in Lung Tumorigenesis.


Source: Chinese Academy of Sciences; Photo: Shutterstock.
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