YBX1 knockdown induces renal cell carcinoma cell apoptosis via Kindlin-2.

Abstract

Among urological tumors, renal cell carcinoma (RCC) is the third-highest mortality rate tumor, and 20%-30% of RCC patients present with metastases at the time of diagnosis. While the treatment of RCC has been improved over the last few years, its mortality stays high. Y-box binding protein 1 (YBX1) is a well-known oncoprotein that has tumor-promoting functions. YBX1 is widely considered to be an attractive therapeutic target in cancer. To develop novel therapeutics to target YBX1, it is of great importance to understand how YBX1 is finely regulated in cancer. Our previous studies showed that YBX1 in RCC cells significantly promoted cell adhesion, migration, and invasion. However, the role of YBX1 in RCC cells apoptosis has not been reported. In this study, we investigated the effect of YBX1 on cell apoptosis and elucidated the mechanisms involved. Results showed that YBX1 regulated RCC cells apoptosis and reactive oxygen species (ROS) generation via Kindlin-2. These findings indicated that YBX1 inhibited RCC cells apoptosis and may serve as a candidate RCC prognostic marker and a potential therapeutic target. Abbreviations: RCC: Renal cell carcinoma; YBX1: Y-box binding protein 1; ROS: Reactive oxygen species; ccRCC: Clear cell renal cell carcinoma; mccRCC: Metastatic clear cell renal cell carcinoma; G3BP1: Ras-GTPase activating protein SH3 domain-binding proteins 1; SPP1: Secreted phosphoprotein 1; NF-κB: Nuclear factor kappa beta; ECM: Extracellular matrix; EMT: Epithelial-mesenchymal transition; PYCR1: Pyrroline-5-carboxylate reductase 1; MEM: Eagle's Minimum Essential Medium; DMEM: Dulbecco's modified Eagle medium; FBS: Fetal bovine serum; PCR: Polymerase chain reaction; shRNA: Short hairpin RNA; siRNA: Small interfering RNA; BSA: Bovine serum albumin; DCFH-DA: 2,7-Dichlorodihydrofluorescein diacetate; FITC: Fluorescein isothiocyanate; PI: Propidium iodide.

• Authors: Qiqi Cui, Chao Wang, Shuang Liu, Runxuan Du, Shaoping Tian, Ruibing Chen, Hua Geng, Saravanan Subramanian, Yuanjie Niu, Yong Wang, Dan Yue
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 20 Issue 22 Pg. 2413-2427 (11 2021) ISSN: 1551-4005 [Electronic] United States
• PMID: 34709966 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• FERMT2 protein, human
• Membrane Proteins
• Neoplasm Proteins
• Poly-ADP-Ribose Binding Proteins
• RNA Recognition Motif Proteins
• Y-Box-Binding Protein 1
• YBX1 protein, human
• DNA Helicases
• G3BP1 protein, human
• RNA Helicases

Topics

• Apoptosis (genetics)
• Carcinoma, Renal Cell (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• DNA Helicases (metabolism)
• Gene Knockdown Techniques
• Humans
• Kidney Neoplasms (genetics, metabolism, pathology)
• Membrane Proteins
• Neoplasm Proteins
• Poly-ADP-Ribose Binding Proteins (metabolism)
• RNA Helicases (metabolism)
• RNA Recognition Motif Proteins (genetics)
• Y-Box-Binding Protein 1 (genetics)