YBX1 mediates autophagy by targeting p110β and decreasing the sensitivity to cisplatin in NSCLC.

Abstract

Y-box binding protein 1 (YBX1) is involved in the development of multiple types of tumors. However, the relationship between YBX1 and autophagy in non-small cell lung cancer (NSCLC) remains unclear. In this study, we analyzed the expression and clinical significance of YBX1 and markers of autophagy (LC3I/II) in NSCLC and examined their roles in regulating sensitivity to cisplatin in NSCLC. The retrospective analysis of patients with NSCLC indicated that YBX1 was positively correlated with autophagy. Increased levels of YBX1 or autophagy also observed in NSCLC cells compared with those in 16HBE cells. Compared to the controls, the knockdown of YBX1 expression suppressed autophagy, increased drug sensitivity and promoted apoptosis in response to cisplatin in NSCLC cells by targeting the p110β promoter and inhibiting p110β/Vps34/beclin1 signaling pathways. We also demonstrated in an in vivo study that the overexpressed YBX1 effectively increased NSCLC growth and progression and decreased the sensitivity to cisplatin by inducing autophagy in a xenograft tumor model, and these effects were concomitant with the increasing of p110β and beclin1 expression. Collectively, these results show that YBX1 plays an essential role in autophagy in NSCLC.

• Authors: Yanwei Cui, Fengzhou Li, Qiang Xie, Shilei Zhao, Tao Guo, Ping Guo, Sheng Hu, Jiaojiao Hao, Chunfang Tian, Wendan Yu, Zhuoshi Li, Lei Fang, Lei Zhao, Manyu Chen, Taihua Wu, Chundong Gu
• Journal: Cell death & disease (Cell Death Dis) Vol. 11 Issue 6 Pg. 476 (06 19 2020) ISSN: 2041-4889 [Electronic] England
• PMID: 32561752 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Beclin-1
• MAP1LC3A protein, human
• Microtubule-Associated Proteins
• Y-Box-Binding Protein 1
• YBX1 protein, human
• Class Ia Phosphatidylinositol 3-Kinase
• Cisplatin

Topics

• Aged
• Aged, 80 and over
• Animals
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Beclin-1 (metabolism)
• Carcinoma, Non-Small-Cell Lung (drug therapy, enzymology, pathology, ultrastructure)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cisplatin (pharmacology, urine)
• Class Ia Phosphatidylinositol 3-Kinase (metabolism)
• Disease Models, Animal
• Female
• Humans
• Lung Neoplasms (drug therapy, enzymology, pathology, ultrastructure)
• Male
• Mice, Inbred BALB C
• Mice, Nude
• Microtubule-Associated Proteins (metabolism)
• Middle Aged
• Y-Box-Binding Protein 1 (metabolism)