Overexpression of ribonuclease inhibitor induces autophagy in human colorectal cancer cells via the Akt/mTOR/ULK1 pathway.

Abstract

Ribonuclease inhibitor (RI), also termed angiogenin inhibitor, acts as the inhibitor of ribonucleolytic activity of RNase A and angiogenin. The expression of RI has been investigated in melanoma and bladder cancer cells. However, the precise role of RI in tumorigenesis, in addition to RI-induced autophagy, remains poorly understood. In the present study, it was demonstrated that RI positively regulated autophagy in human colorectal cancer (CRC) cells as indicated by an increase in light chain 3 (LC3)-II levels. Furthermore, RI regulated cell survival in HT29 cells. In addition, autophagy-associated proteins, including beclin-1 and autophagy-related protein 13, were increased in response to RI-induced autophagy, and the protein kinase B (Akt)/mechanistic target of rapamycin (mTOR)/Unc-51 like autophagy activating kinase (ULK1) pathway may be involved in the activation of autophagy induced by RI overexpression. Taken together, the evidence of the present study indicated that the overexpression of RI induced ATG-dependent autophagy in CRC cells via the Akt/mTOR/ULK1 pathway, suggesting that the upregulation of RI activity may constitute a novel approach for the treatment of human colorectal carcinoma.