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Publication : DANCR deletion retards the initiation and progression of hepatocellular carcinoma based on gene knockout and patient-derived xenograft in situ hepatoma mice model.

First Author  Gan X Year  2022
Journal  Cancer Lett Volume  550
Pages  215930 PubMed ID  36183859
Mgi Jnum  J:329926 Mgi Id  MGI:7355821
Doi  10.1016/j.canlet.2022.215930 Citation  Gan X, et al. (2022) DANCR deletion retards the initiation and progression of hepatocellular carcinoma based on gene knockout and patient-derived xenograft in situ hepatoma mice model. Cancer Lett 550:215930
abstractText  Our previous study has demonstrated that the expression level of long noncoding RNA (lncRNA)-differentiation antagonizing non-protein coding RNA (DANCR) increases in hepatocellular carcinoma (HCC), contributing to the initiation and aggravation of such kind of malignant tumor, which is recognized as a promising therapeutic target for patients with HCC. To further investigate the effect of DANCR on HCC in preclinical models, we generated a Dancr knockout (KO) mice model by Cas9/gRNA technology and a patient-derived xenograft (PDX) in situ hepatoma mice model using immunodeficient mice and utilized adeno-associated virus 8 (AAV8) delivery DANCR-shRNA system to silence the expression of DANCR in xenograft tumor. Here, we reported that Dancr expression mainly occurred in hepatocytes and its depletion significantly alleviated hepatic fibrosis in mice and showed a prospective result with smaller tumor size and fewer number of tumors in HCC preclinical mice model. Additionally, we found that the expression of Dancr in mice cirrhotic liver was positively correlated with the content of Dancr in serum. Overall, DANCR KO can inhibit the occurrence and development of HCC and is a target worthy of further study in patients with HCC.
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