YBX1 mediates autophagy by targeting p110\u03b2 and decreasing the sensitivity to cisplatin in NSCLC

Yanwei Cui,Taihua Wu,Manyu Chen,Ping Guo,Qiang Xie,Fengzhou Li,Wendan Yu,Jiaojiao Hao,Lei Zhao,Shilei Zhao,Sheng Hu,Tao Guo,Chundong Gu,Lei Fang,Chunfang Tian,Zhuoshi Li

doi:10.1038/s41419-020-2555-4

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.

Highlights

Lung cancer, a malignant lung tumor with uncontrolled cell growth in the lung tissue, is the main cause of cancer death worldwide[1,2]
The results showed that Y-box binding protein 1 (YBX1) and LC3I/II cohighly expressed in tumor cell lines or Non-small cell lung cancer (NSCLC) tissues compared to their corresponding adjacent normal cells or normal tissues
The results showed that knockdown YBX1 effectively downregulated LC3I/II protein expression compared to the control, in contrast, the overexpression of YBX1 caused an increase of LC3I/II compared to the control (Fig. 2a–d)

Summary

Introduction

A malignant lung tumor with uncontrolled cell growth in the lung tissue, is the main cause of cancer death worldwide[1,2]. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancers[3]. Patients with lung cancer have short average survival time from the time of diagnosis. Because curative treatment is not usually feasible due to tumor dissemination, invasion, distant metastases and limited sensitivity to chemotherapeutic drugs[4]. Poor prognosis is closely related to drug insensitivity in NSCLC. Investigating mechanisms to increase the sensitivity to antitumor drugs in NSCLC has become urgent

Methods

Results

Conclusion