Published online Oct 6, 2022. doi: 10.12998/wjcc.v10.i28.10017
Peer-review started: December 13, 2021
First decision: April 16, 2022
Revised: April 28, 2022
Accepted: August 25, 2022
Article in press: August 25, 2022
Published online: October 6, 2022
Processing time: 288 Days and 10.5 Hours
Insulin-like growth factor-1 receptor (IGF-1R) is over-expressed in hepatocellular carcinoma (HCC). However, the relationship between IGF-1R activation and HCC progression remains unidentified.
To investigate the effects of editing IGF-1R on the biological features of HCC cells.
Immunohistochemistry analyzed the expressions of IGF-1R and P-glyco protein (P-gp) in HCC tissues and their distal non-cancerous tissues (non-Ca). IGF-1R was edited with Crispr/Cas9 system, screened specific sgRNAs, and then transfected into HepG2 cells. CCK-8, scratch wound test detected cell proliferation, migration, invasion and transwell assays, respectively. Alterations of IGF-1R and P-gp were confirmed by Western blotting. Alterations of anti-cancer drug IC50 values were analyzed at the cell level.
The positive rates of IGF-1R (93.6%, χ2 = 63.947) or P-gp (88.2%, χ2 = 58.448) were significantly higher (P < 0.001) in the HCC group than those (36.6% in IGF-1R or 26.9% in P-gp) in the non-Ca group. They were positively correlated between high IGF-1R and P-gp expression, and they were associated with hepatitis B virus infection and vascular invasion of HCC. Abnormal expressions of circulating IGF-1R and P-gp were confirmed and associated with HCC progression. Biological feature alterations of HCC cells transfected with specific sgRNA showed IGF-1R expression down-regulation, cell proliferation inhibition, cell invasion or migration potential decreasing, and enhancing susceptibility of HepG2 cells to anti-cancer drugs.
Edited oncogenic IGF-1R was useful to inhibit biological behaviors of HepG2 cells.
Core Tip: Abnormal expression of insulin-like growth factor-1 receptor (IGF-1R) was associated with hepatocellular carcinoma (HCC). IGF-1R level was significantly higher in HCC more than that in their noncancerous tissues. Circulating IGF-1R continued to increase from benign liver disease to HCC. Down-regulating expression of IGF-1R with a specific sgRNA was markedly affected on biological behaviors of HCC cells, including inhibiting cell proliferation, decreasing cell migration or invasion potential, increasing cell apoptosis and enhancing cell susceptibility to anti-tumor drugs and indicated that oncogenic IGF-1R should be a promising targeted-molecule for HCC therapy.