Research Paper Volume 15, Issue 4 pp 1210—1227
Inhibition of apoptosis through AKT-mTOR pathway in ovarian cancer and renal cancer
- 1 Department of Urology, China Aerospace Science and Industry Corporation 731 Hospital, Beijing 100074, China
- 2 Department of Social Work, The First People's Hospital of Fuyang District of Hangzhou, Hangzhou 311400, Zhejiang, China
- 3 Department of Urology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei, China
Received: November 23, 2022 Accepted: February 11, 2023 Published: February 27, 2023
https://doi.org/10.18632/aging.204564How to Cite
Copyright: © 2023 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Objective: Ovarian cancer and renal cancer are malignant tumors; however, the relationship between TTK Protein Kinase (TTK), AKT-mTOR pathway and ovarian cancer, renal cancer remains unclear.
Methods: Download GSE36668 and GSE69428 from Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was performed. Created protein-protein interaction (PPI) network. Used Gene Ontology analysis (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for functional enrichment analysis. Gene Set Enrichment Analysis (GSEA) analysis and survival analysis were performed. Created animal model for western blot analysis. Gene Expression Profiling Interactive Analysis (GEPIA) was performed to explore the role of TTK on the overall survival of renal cancer.
Results: GO showed that DEGs were enriched in anion and small molecule binding, and DNA methylation. KEGG analysis presented that they mostly enriched in cholesterol metabolism, type 1 diabetes, sphingolipid metabolism, ABC transporters, etc., TTK, mTOR, p-mTOR, AKT, p-AKT, 4EBP1, p-4EBP1 and Bcl-2 are highly expressed in ovarian cancer, Bax, Caspase3 are lowly expressed in ovarian cancer, cell apoptosis is inhibited, leading to deterioration of ovarian cancer. Furthermore, the TTK was not only the hub biomarker of ovarian cancer, but also one significant hub gene of renal cancer, and its expression was up-regulated in the renal cancer. Compared with the renal cancer patients with low expression of TTK, the patients with high expression of TTK have the poor overall survival (P = 0.0021).
Conclusion: TTK inhibits apoptosis through AKT-mTOR pathway, worsening ovarian cancer. And TTK was also one significant hub biomarker of renal cancer.
Abbreviations
GEO: gene expression omnibus; WGCNA: weighted gene co-expression network analysis; PPI: protein-protein interaction; GO: Gene Ontology analysis; KEGG: Kyoto Encyclopedia of Genes and Genomes; GSEA: Gene Set Enrichment Analysis; DEGs: differentially expressed Genes; MCODE: Molecular Complex Detection; TTK: TTK Protein Kinase; FC: Fold change; FDR: false discovery rate; MAD: Median Absolute Deviation; TOM: topological overlap matrix; STRING: Search Tool for the Retrieval of Interacting Genes; WB: Western Blot; mTOR: Mammalian Target of Rapamycin.