Abstract: Objective To explore the mechanism and potential regulation of GP73 in human colorectal cancer cell proliferation. Methods GEPIA website was used to analyze GP73 gene expression in human colorectal cancer samples. shRNA targeting GP73 was constructed and then transfected into Caco2 and HT-29 cells to knock-down GP73 expression. Cell proliferation was measured by CCK8 assay. Colony formation experiment was used to detect cell proliferation. CCK8 method was used to detect control cells and GP73-knockdown HT-29 cell proliferation after rapamycin treatment. Wild type mice administered with AOM-DSS induced colitis-associated colorectal cancer (CAC) were treated with rapamycin. Western blot was used to detect protein levels of mTOR and GP73 pathway in treated mice. Results GP73 is highly expressed in human colorectal cancer tissues. Deficient-GP73 inhibited human colorectal cancer cell proliferation. Rapamycin suppressed AOM-DSS induced CAC development and down regulated mTOR-GP73 axis. Down-regulation of GP73 caused human colorectal cancer cells insensitive to rapamycin treatment. Conclusions GP73 is highly expressed in human colorectal cancer tissues. Deficient-GP73 inhibits proliferation of human colorectal cancer cells. Rapamycin inhibits the progression of colorectal cancer through down-regulation of mTOR-GP73 pathway.

Key words: colorectal cancer, mTOR, GP73