CXCR3 gene as a therapeutic target in colorectal cancer
Seyedeh Zohreh Azarshin1, Melina Malmir1, Seyedeh Fatemeh Sajjadi1
1Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, P.O. Box: 14115-154, Tehran, Iran.
Background:
Cancers, especially colorectal cancer, are among the most common and deadly diseases in the world, and their incidence is increasing in various countries. Current therapeutic methods, such as chemotherapy, surgery, and immunotherapy, have failed to provide successful treatment without side effects. Therefore, identifying effective therapeutic targets is crucial. Several studies have demonstrated that the expression of the CXCR3 gene, a member of the GPCR family, is elevated in colorectal cancer.
Methods:
In this study, the effect of targeting the CXCR3 gene on the HCT-116 line, a colorectal cancer cell line, was investigated via gene-specific targeting. For this purpose, specific DNAzymes were designed, and the impact of CXCR3 downregulation on cancer cell development was assessed via cell cycle analysis, Annexin V-PI staining, and the wound healing method.
Results:
CXCR3 gene downregulation inhibited the key AKT‒MTOR pathway and reduced proliferation and growth of HCT-116 cells. Moreover, CXCR3 mRNA downregulation increased the apoptosis of these cells.
Conclusion:
Our findings suggest that downregulation of CXCR3 mRNA inhibits colorectal cancer cell growth through inhibition of the AKT‒mTOR pathway. The CXCR3 receptor can be considered a new therapeutic target in colorectal cancer therapy.
