PMID- 30896869 OWN - NLM STAT- MEDLINE DCOM- 20190801 LR - 20211204 IS - 1791-3004 (Electronic) IS - 1791-2997 (Print) IS - 1791-2997 (Linking) VI - 19 IP - 5 DP - 2019 May TI - Overexpression of ribonuclease inhibitor induces autophagy in human colorectal cancer cells via the Akt/mTOR/ULK1 pathway. PG - 3519-3526 LID - 10.3892/mmr.2019.10030 [doi] AB - 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. FAU - Tang, Ying AU - Tang Y AD - Department of Pathology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China. FAU - Ren, Feng AU - Ren F AD - Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China. FAU - Cong, Xi AU - Cong X AD - Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China. FAU - Kong, Ying AU - Kong Y AD - Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China. FAU - Tian, Yuxiang AU - Tian Y AD - Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China. FAU - Xu, Yuefei AU - Xu Y AD - Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China. FAU - Fan, Jianhui AU - Fan J AD - Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China. LA - eng PT - Journal Article DEP - 20190314 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Placental Hormones) RN - 120178-77-0 (placental ribonuclease inhibitor) RN - EC 2.7.11.1 (Autophagy-Related Protein-1 Homolog) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.1 (ULK1 protein, human) MH - Autophagy/genetics MH - Autophagy-Related Protein-1 Homolog/*metabolism MH - Cell Line, Tumor MH - Cell Survival/genetics MH - Colorectal Neoplasms/*genetics/*metabolism/pathology MH - *Gene Expression MH - HT29 Cells MH - Humans MH - Intracellular Signaling Peptides and Proteins/*metabolism MH - Placental Hormones/*genetics MH - Proto-Oncogene Proteins c-akt/*metabolism MH - *Signal Transduction MH - TOR Serine-Threonine Kinases/*metabolism PMC - PMC6472130 EDAT- 2019/03/22 06:00 MHDA- 2019/08/02 06:00 PMCR- 2019/03/14 CRDT- 2019/03/22 06:00 PHST- 2018/06/19 00:00 [received] PHST- 2019/03/06 00:00 [accepted] PHST- 2019/03/22 06:00 [pubmed] PHST- 2019/08/02 06:00 [medline] PHST- 2019/03/22 06:00 [entrez] PHST- 2019/03/14 00:00 [pmc-release] AID - mmr-19-05-3519 [pii] AID - 10.3892/mmr.2019.10030 [doi] PST - ppublish SO - Mol Med Rep. 2019 May;19(5):3519-3526. doi: 10.3892/mmr.2019.10030. Epub 2019 Mar 14.