CRISPR/Cas9-mediated genome engineering of CXCR4 decreases the malignancy of hepatocellular carcinoma cells in vitro and in vivo.

Abstract:

:CXC chemokine receptor 4 (CXCR4) is associated with poor clinical outcomes and decreased survival in hepatocellular carcinoma (HCC). In the present study, we targeted CXCR4 by CRISPR/Cas9 in HepG2 cells and observed the effects both in vitro and in vivo. The results indicated that after targeting CXCR4 the expression of CXCR4 was significantly decreased and the cell proliferation was inhibited. Clonogenicity and scratch cell migration assays indicated that specific downregulation of CXCR4 inhibited cell migration. This disruption of CXCR4 led to less invasiveness, the genes related to epithelial-mesenchymal transition (EMT) and cell self-renewal were also affected. Moreover, sensitivity to the anticancer drug cisplatin was significantly increased in vitro by the downregulation of CXCR4. The results of the in vivo study showed that the growth volumes were significantly smaller in neoplasms derived from CXCR4-downregulated HepG2 cells compared to those derived from wild-type cells. These results showed that targeting CXCR4 by CRISPR/Cas9 could inhibit proliferation, migration and invasion, reversed EMT, increased chemosensitivity and decrease the malignancy of HCC in vitro and in vivo.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Wang X,Zhang W,Ding Y,Guo X,Yuan Y,Li D

doi

10.3892/or.2017.5601

subject

Has Abstract

pub_date

2017-06-01 00:00:00

pages

3565-3571

issue

6

eissn

1021-335X

issn

1791-2431

journal_volume

37

pub_type

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