Department of Pathology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China.
Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
Mol Med Rep. 2019 May;19(5):3519-3526. doi: 10.3892/mmr.2019.10030. Epub 2019 Mar 14.
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.
核糖核酸酶抑制剂 (RI)，也称为血管生成素抑制剂，作为核糖核酸酶 A 和血管生成素的核糖核酸酶活性抑制剂。RI 的表达已在黑色素瘤和膀胱癌细胞中进行了研究。然而，除了 RI 诱导的自噬之外，RI 在肿瘤发生中的精确作用仍知之甚少。在本研究中，证明 RI 可通过增加 LC3-II 水平来正向调节人结直肠癌细胞中的自噬。此外，RI 调节 HT29 细胞中的细胞存活。此外，自噬相关蛋白，包括 beclin-1 和自噬相关蛋白 13，响应 RI 诱导的自噬而增加，并且蛋白激酶 B (Akt)/雷帕霉素机制靶蛋白 (mTOR)/UNC-51 样自噬激活激酶 (ULK1) 途径可能参与 RI 过表达诱导的自噬的激活。综上所述，本研究的证据表明，RI 的过表达通过 Akt/mTOR/ULK1 途径诱导 CRC 细胞中的 ATG 依赖性自噬，表明 RI 活性的上调可能构成治疗人类结直肠癌的新方法。
