YBX1 regulates tumor growth via CDC25a pathway in human lung adenocarcinoma.

Abstract

Y-box binding protein 1 (YBX1) is involved in the multi-tumor occurrence and development. However, the regulation of YBX1 in lung tumorigenesis and the underlying mechanisms, especially its relationship with CDC25a, was remains unclear. In this study, we analyzed the expression and clinical significance of YBX1 and CDC25a in lung adenocarcinoma and identified their roles in the regulation of lung cancer growth. The retrospective analysis of 116 patients with lung adenocarcinoma indicated that YBX1 was positively correlated with CDC25a expression. The Cox-regression analysis showed only high-ranking TNM stage and low CDC25a expression were an independent risk factor of prognosis in enrolled patients. High expression of YBX1 or CDC25a protein was also observed in lung adenocarcinoma cells compared with HLF cells. ChIP assay demonstrated the binding of endogenous YBX1 to the CDC25a promoter region. Overexpression of exogenous YBX1 up-regulated the expression of the CDC25a promoter-driven luciferase. By contrast, inhibition of YBX1 by siRNA markedly decreased the capability of YBX1 binding to CDC25a promoter in A549 and H322 cells. Inhibition of YBX1 expression also blocked cell cycle progression, suppressed cell proliferation and induced apoptosis via the CDC25a pathway in vitro. Moreover, inhibition of YBX1 by siRNA suppressed tumorigenesis in a xenograft mouse model and down-regulated the expression of YBX1, CDC25a, Ki67 and cleaved caspase 3 in the tumor tissues of mice. Collectively, these results demonstrate inhibition of YBX1 suppressed lung cancer growth partly via the CDC25a pathway and high expression of YBX1/CDC25a predicts poor prognosis in human lung adenocarcinoma.

• Authors: Shilei Zhao, Yan Wang, Tao Guo, Wendan Yu, Jinxiu Li, Zhipeng Tang, Zhenlong Yu, Lei Zhao, Yixiang Zhang, Ziyi Wang, Peng Wang, Yechi Li, Fengzhou Li, Zhe Sun, Yang Xuan, Ranran Tang, Wu-Guo Deng, Wei Guo, Chundong Gu
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 50 Pg. 82139-82157 (Dec 13 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27384875 (Publication Type: Journal Article)

Chemical References

• Ki-67 Antigen
• Y-Box-Binding Protein 1
• YBX1 protein, human
• CDC25A protein, human
• cdc25 Phosphatases
• CASP3 protein, human
• Caspase 3

Topics

• A549 Cells
• Adenocarcinoma (enzymology, genetics, mortality, pathology)
• Adenocarcinoma of Lung
• Aged
• Aged, 80 and over
• Animals
• Apoptosis
• Binding Sites
• Caspase 3 (genetics, metabolism)
• Cell Movement
• Cell Proliferation
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Ki-67 Antigen (genetics, metabolism)
• Lung Neoplasms (enzymology, genetics, mortality, pathology)
• Male
• Mice, Nude
• Middle Aged
• Neoplasm Staging
• Promoter Regions, Genetic
• Proportional Hazards Models
• RNA Interference
• Signal Transduction
• Time Factors
• Transfection
• Tumor Burden
• Y-Box-Binding Protein 1 (genetics, metabolism)
• cdc25 Phosphatases (genetics, metabolism)