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

Oncology Reports
Xiaoli WangDong Sheng Li

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.

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Citations

Nov 21, 2019·International Journal of Molecular Medicine·Zhongrong GuoYuanliang Huang
Sep 8, 2019·Journal of Experimental & Clinical Cancer Research : CR·Xing Rong GuoDong Sheng Li
Nov 16, 2019·Journal of Experimental & Clinical Cancer Research : CR·Shuhua ZhangJianqun Xu
Feb 3, 2020·Cellular and Molecular Life Sciences : CMLS·Reza MohammadinejadIman Azimi
Jan 3, 2021·Molecular Biotechnology·Precilla S DaisyT S Anitha
Apr 17, 2021·Cancer Gene Therapy·Vijayata SinghGiridhara R Jayandharan
Aug 14, 2021·Frontiers in Cell and Developmental Biology·Sheng WangXiongwen Lv

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